Repeated HyperArc radiosurgery for recurrent intracranial metastases and dosimetric analysis of recurrence pattern to account for diffuse dose effect on microscopical disease.

Aims: Evaluate effectiveness and safety of multiple HyperArc courses and patterns of progression in patients affected by BMs with intracranial progression. Methods: 56 patients were treated for 702 BMs with 197 (range 2-8) HyperArc courses in case of exclusive intracranial progression. Primary end-point was the overall survival (OS), secondary end-points were intracranial progression-free survival (iPFS), toxicity, local control (LC), neurological death (ND), and whole-brain RT (WBRT)-free survival. Site of progression was evaluated against isodoses levels (0, 1, 2, 3, 5, 7, 8, 10, 13, 15, 20, and 24 Gy.). Results: The 1-year OS was 70 %, and the median was 20.8 months (17-36). At the univariate analysis (UVA) biological equivalent dose (BED) > 51.3 Gy and non-melanoma histology significantly correlated with OS. The median time to iPFS was 4.9 months, and the 1-year iPFS was 15 %. Globally, 538 new BMs occurred after the first HA cycle in patients with extracranial disease controlled. 96.4 % of them occurred within the isodoses range 0-7 Gy as follows: 26.6 % (0 Gy), 16.5 % (1 Gy), 16.5 % (2 Gy), 20.1 % (3 Gy), 13.1 % (5 Gy), 3.4 % (7 Gy) (p = 0.00). Radionecrosis occurred in 2 metastases (0.28 %). No clinical toxicity of grade 3 or higher occurred during follow-up. One- and 2-year LC was 90 % and 79 %, respectively. At the UVA BED > 70 Gy and non-melanoma histology were significant predictors of higher LC. The 2-year WBRT-free survival was 70 %. After a median follow-up of 17.4 months, 12 patients deceased by ND. Conclusion: Intracranical relapses can be safely and effectively treated with repeated HyperArc, with the aim to postpone or avoid WBRT. Diffuse dose by volumetric RT might reduce microscopic disease also at relatively low levels, potentially acting as a virtual CTV. Neurological death is not the most common cause of death in this population, which highlights the impact of extracranial disease on overall survival.

Prostate volume variation during 1.5T MR-guided adaptive stereotactic body radiotherapy (SBRT) and correlation with treatment toxicity.

INTRODUCTION: To evaluate prostate volume change during daily-adaptive prostate SBRT on 1.5 T MR-linac and to correlate it with treatment toxicity. METHODS: a series of patients affected by low-to-intermediate risk prostate cancer was treated by 5-fraction SBRT within a prospective study (Prot. n° 23748). Total dose was 35 Gy and 36.25 Gy delivered every day or on alternate days. Treatment toxicity was recorded with the following patient reported outcomes (PROMs): IPSS, ICIQ-SF, and EPIC-26. RESULTS: 254 patients were included in the analysis. Baseline median CTV volume was 55 cc (range 15.3-163.3). Mean prostate volume were 58.9 cc, and 62.7 cc at first and last fraction respectively (mean volume increase 6.4 %; p = <0.0001). We observed prostate swelling (mean 15.4 % increase) in 50 % of cases, stable volume (≤5% volume change) in 39 % of patients, and prostate shrinkage in 11 % of cases (mean 12.2 % reduction). Baseline CTV > 55 cc showed a trend towards higher CTV shrinkage (-10.5 % versus -14.5 %; p = 0.052). We found no correlation between CTV change and PROMs. Prostate swelling was generally compensated by the planned PTV expansion, even though the mean setup volume dropped from 47.4 cc to 38.9 cc at last fraction, with few cases not covered by initial setup margins. CONCLUSION: The present study reported a significant prostate volume change during prostate SBRT on 1.5T MR-linac. We observed both prostate swelling in half of cases and few cases of prostate shrinkage. No correlations were found with PROMs in this population treatment with daily-adaptive strategy.

PSMA-PET/CT-Based Stereotactic Body Radiotherapy (SBRT) in the Treatment of Uncomplicated Non-Spinal Bone Oligometastases from Prostate Cancer.

BACKGROUND AND PURPOSE: Stereotactic body radiotherapy (SBRT) has a consolidated role in the treatment of bone oligometastases from prostate cancer (PCa). While the evidence for spinal oligometastases SBRT was robust, its role in non-spinal-bone metastases (NSBM) is not standardized. In fact, there was no clear consensus about dose and target definition in this setting. The aim of our study was to evaluate efficacy, toxicity, and the pattern of relapse in SBRT delivered to NSBM from PCa. MATERIALS AND METHODS: From 2016 to 2021, we treated a series of oligo-NSBM from PCa with 68Ga-PSMA PET/CT-guided SBRT. The primary endpoint was local progression-free survival (LPFS). The secondary endpoints were toxicity, the pattern of intraosseous relapse, distant progression-free survival (DPFS), polimetastases-free survival (PMFS), and overall survival (OS). RESULTS: a total of 150 NSBM in 95 patients were treated with 30-35 Gy in five fractions. With a median follow-up of 26 months, 1- and 3 years LPFS was 96.3% and 89%, respectively. A biologically effective dose (BED) ≥ 198 Gy was correlated with improved LPFS (p = 0.007). Intraosseous relapse occurred in eight (5.3%) cases. Oligorecurrent disease was associated with a better PMFS compared to de novo oligometastatic disease (p = 0.001) and oligoprogressive patients (p = 0.007). No grade ≥ 3 toxicity occurred. CONCLUSION: SBRT is a safe and effective tool for NSBM from PCa in the oligometastatic setting. Intraosseous relapse was a relatively rare event. Predictive factors of the improved outcomes were defined.

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.

Analysis of tumour dose-response data from animal experiments via two TCP models accounting for tumor hypoxia and resensitization.

To treat animal dose-response data exhibiting inverse dose-response behavior with two tumor control probability (TCP) models accounting for tumor hypoxia and re-oxygenation leading to resensitization of the tumor. One of the tested TCP models uses a modified linear-quadratic (LQ) model of cell survival where both α and ß radiosensitivities increase in time during the treatment due to re-oxygenation of the hypoxic tumor sub-population. The other TCP model deals with two types of hypoxia-chronic and acute-and accounts for tumor re-sensitization via oxygenation of the chronically hypoxic and fluctuating oxygenation of the acutely hypoxic sub-populations. The two models are fit using the maximum likelihood method to the data of Fowler et al. on mice mammary tumors irradiated to different doses using different fractionated schedules. These data are chosen since as many as five of the dose-response curves show an inverse dose behavior, which is interpreted as due to re-sensitization. The p-values of the fits of both models to the data render them statistically acceptable. A performed comparison test shows that both models describe the data equally well. It is also demonstrated that the most sensitive (oxic) tumor component has no impact on the treatment outcome. The ability of the tested models to predict and describe the impact of re-sensitization on the treatment outcome is thus proven. It is also demonstrated that prolonged treatment schedules can be more beneficial than shorter ones. However, this may be true only for schedules with small number of fractions, i.e. for hypo-fractionated treatments only.

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.

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.

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.

A novel treatment for malignant spasticity: The therapeutic use of stereotactic radiosurgery (SRS).

Spasticity is a clinical condition secondary to central nervous system damage, which impairs patients' mobility and quality of life. Stereotactic radiosurgery (SRS) to the spinal roots responsible of the spasms might represent a non-invasive therapy. The present are the preliminary results of the first clinical use of this novel technique.

Radiomic analysis to predict local response in locally advanced pancreatic cancer treated with stereotactic body radiation therapy.

PURPOSE: Aim of this study is to assess the ability of contrast-enhanced CT image-based radiomic analysis to predict local response (LR) in a retrospective cohort of patients affected by pancreatic cancer and treated with stereotactic body radiation therapy (SBRT). Secondary aim is to evaluate progression free survival (PFS) and overall survival (OS) at long-term follow-up. METHODS: Contrast-enhanced-CT images of 37 patients who underwent SBRT were analyzed. Two clinical variables (BED, CTV volume), 27 radiomic features were included. LR was used as the outcome variable to build the predictive model. The Kaplan-Meier method was used to evaluate PFS and OS. RESULTS: Three variables were statistically correlated with the LR in the univariate analysis: Intensity Histogram (StdValue feature), Gray Level Cooccurrence Matrix (GLCM25_Correlation feature) and Neighbor Intensity Difference (NID25_Busyness feature). Multivariate model showed GLCM25_Correlation (P = 0.007) and NID25_Busyness (P = 0.03) as 2 independent predictive variables for LR. The odds ratio values of GLCM25_Correlation and NID25_Busyness were 0.07 (95%CI 0.01-0.49) and 8.10 (95%CI 1.20-54.40), respectively. The area under the curve for the multivariate logistic regressive model was 0.851 (95%CI 0.724-0.978). At a median follow-up of 30 months, median PFS was 7 months (95%CI 6-NA); median OS was 11 months (95%CI 10-22 months). CONCLUSIONS: This analysis identified a radiomic signature that correlates with LR. To confirm these results, prospective studies could identify patient sub-groups with different rates of radiation dose-response to define a more personalized SBRT approach.

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.

The Impact of Different Timing Schedules on Prostate HDR-Mono-Brachytherapy. A TCP Modeling Investigation.

BACKGROUND: Mechanistic TCP (tumor control probability) models exist that account for possible re-sensitization of an initially hypoxic tumor during treatment. This phenomenon potentially explains the better outcome of a 28-day vs 14-day treatment schedule of HDR (high dose rate) brachytherapy of low- to intermediate-risk prostate cancer as recently reported. METHODS: A TCP model accounting for tumor re-sensitization developed earlier is used to analyze the reported clinical data. In order to analyze clinical data using individual TCP model, TCP distributions are constructed assuming inter-individual spread in radio-sensitivity. RESULTS: Population radio-sensitivity parameter values are found that result in TCP population values which are close to the reported ones. Using the estimated population parameters, two hypothetical regimens are investigated that are shorter than the ones used clinically. The impact of the re-sensitization rate on the calculated treatment outcome is also investigated as is the anti-hypothesis that there is no re-sensitization during treatment. CONCLUSIONS: The carried out investigation shows that the observed clinical data cannot be described without assuming an initially hypoxic state of the tumor followed by re-oxygenation and, hence, re-sensitization. This phenomenon explains the better outcome of the prolonged treatment schedule compared to shorter regimens based on the fact that prostate cancer is a slowly repopulating tumor.

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.

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.

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.