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Luca Nicosia,1 Claudio Vitale,1 Francesco Cuccia,1 Vanessa Figlia,1 Niccolò Giaj-Levra,1 Rosario Mazzola,1 Francesco Ricchetti,1 Michele Rigo,1 Ruggero Ruggieri,1 Stefano Cavalleri,2 Filippo Alongi1,3 1Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, Verona, Negrar, Italy; 2Urology Division, IRCCS Sacro Cuore Don Calabria Hospital, Verona, Negrar, Italy; 3University of Brescia, Brescia, ItalyCorrespondence: Luca Nicosia, Advanced Radiation Oncology Department, IRCCS Sacro Cuore Don Calabria Hospital, Cancer Care Center, via Don Sempreboni 5, 37034, Verona, Negrar, Italy, Tel +39 045-6014800, Fax +045-60148071, Email lucanicosia.rg@gmail.comAim: 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.Keywords: prostate cancer, hyaluronic acid, postoperative radiotherapy, salvage radiotherapy, hypofractionation, toxicity

Background: The present study reports on the outcomes of our mono-institutional experience of Helical Tomotherapy (HT)-based SRT for brain metastases. The use of this linac is less frequently reported for this kind of treatment. Methods: This retrospective study displays a series of patients treated with HT-SRT. The eligibility of using SRT for brain metastases was defined by a Karnofsky performance status of >70, a life expectancy of >6 months, and controlled extra-cranial disease; no SRT was allowed in the case of a number of brain metastases larger than 10. All the cases were discussed by a multidisciplinary board. Toxicity assessments were performed based on CTCAE v5.0. Survival endpoints were assessed using the Kaplan–Meier method, and univariate and multivariate analyses were carried out to identify any potential predictive factor for an improved outcome. Results: Sixty-four lesions in 37 patients were treated using HT-SRT with a median total dose of 30 Gy in five fractions. The median follow-up was 7 months, and the 1- and 2-year LC rates were both 92.5%. The IPFS rates were and 56.75% and 51.35%. The OS rates were 54% and 40%. The UA showed better IPFS rates significantly related to male sex (p = 0.049), a BED12 of ≥42 Gy (p = 0.006), and controlled extracranial disease (p = 0.03); in the MA, a favorable trend towards LC (p = 0.11) and higher BED (p = 0.11) schedules maintained a correlation with improved IPFS rates, although statistical significance was not reached. Conclusions: HT-based SRT for brain metastases showed safety and efficacy in our monoinstiutional experience. Higher RT doses showed statistical significance for improved outcomes of LC and OS.

To evaluate the impact of moderately hypofractionated postoperative radiotherapy (RT) in prostate cancer (PCa).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.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.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.

This retrospective study aims to evaluate the efficacy and safety of salvage HDR brachytherapy in second local recurrences of prostate cancer after applying radical prostatectomy (RP) and post-operative external beam radiotherapy (EBRT).Fifteen patients with locally recurrent prostate cancer after RP and EBRT were salvaged with HDR brachytherapy. Patients had no nodal or distant metastasis evidence on imaging findings, including whole body bone scan, CT scan, and MRI or PSMA PET scan. HDR brachytherapy was applied with 36 Gy in four fractions, in two implantations with 1 week apart. We followed the patients for a control visit every 3 months for 2 years, and every 6 months thereafter.Fifteen patients with the mean age of 64 years (ranged 51-79) underwent salvage HDR brachytherapy. The mean baseline level of PSA was calculated 2.26 ng/ml (ranged from 0.21 to 9, SD = 2.33), which has been significantly decreased in all patients. Hence, two of our patients experienced a biochemical failure during the follow-up period. Our results showed that 86.6% (n = 13) of patients had never experienced a significant increment in PSA level after a median follow-up of 48 months (ranging from 12 to 132 months). Besides, salvage HDR brachytherapy did not induce any significant side effects such as acute or late rectal complications, despite causing urinary complication.HDR brachytherapy could be considered as a treatment in well-selected patients with the second recurrence in their prostatic bed after the former EBRT allowing for dose escalating to the second nodular recurrence.

Cardiac arrhythmias are a leading cause of mortality, morbidity, and sudden cardiac death (SCD). Current treatment strategies for ventricular tachycardia (VT) are effective for many patients; however, in several cases, this does not result in a cure. Despite significant clinical improvements, conventional catheter ablation remains relatively unsuccessful in achieving the best outcomes in some challenging cases. Stereotactic arrhythmia radioablation (STAR), which delivers precise high-dose radiation to well-defined targets with minimal damage to surrounding tissue, is emerging as a new potential treatment option, having the potential to be used for patients at high risk for catheter ablation or who have refractory VT. Ongoing studies and preliminary experiences on f the efficacy of STAR in patients with refractory VT have shown a reduction in VT recurrence and a promising early safety profile. However, STAR is in its infancy, and clinical evidence on its efficacy and safety is limited; thus, conclusions regarding the efficacy of STAR should be drawn with caution. Further investigation of long-term efficacy and tolerability is ongoing to substantiate this promising therapeutic option better. The present review describes the background and general principles, pretreatment procedures, clinical implications, and toxicity of STAR therapy.

As the use of hypofractionation has spread in the setting of curative prostate radiotherapy, few data are available in the post-operative scenario. This study reports a mono-institutional experience of moderate post-operative hypofractionated radiotherapy for prostate cancer. In February 2021, we retrospectively assessed the outcomes of 129 patients who received between April 2013 and May 2020 hypofractionated post-operative radiotherapy using Helical Tomotherapy. Toxicity was assessed using CTCAE criteria v4.0. Survival endpoints were calculated with Kaplan–Meier method. Median age and follow-up were, respectively, 67 years and 43 months. Adjuvant and salvage treatment were delivered to 63.5% and 36.4% of patients to a median total dose of 63.8 Gy (61.6–65.25 Gy) in 29 fractions (2.12–2.25 Gy/fraction). Pelvic lymph-nodes irradiation was performed in 67.4% of cases. ADT was added in 50%. Acute toxicity was: G1 and G2 GU events in 36% and 9.3% of cases; G1 and G2 GI events in 29.4% and 13.9%. Late GU toxicity occurred in 12.4% of cases: 3.1% G1, 7.7% G2 and 1.5% G3 events; GI toxicity consisted of 1.5% G1 and 7.7% G2 events. Biochemical relapse occurred in 26.3% of cases, recording no significant differences between adjuvant and salvage (p = 0.67), with 4- and 5-years bRFS rates of 78.7% and 75.6%. Two patients died of progressive disease and eight for non-oncological causes resulting in 3-years overall survival and cancer-specific survival rates of 98% and 98.4%. Our experience supports the use of moderate hypofractionation for prostate bed radiotherapy, with minimal toxicity and promising results in terms of clinical outcomes.

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 constant evolution of technology has dramatically changed the history of radiation oncology, allowing clinicians to deliver increasingly accurate and precise treatments, moving from 2D radiotherapy to 3D conformal radiotherapy, leading to intensity-modulated image-guided (IMRT-IGRT) and stereotactic body radiotherapy treatments [...]

Background The present analysis aims to compare the impact of 18F-fluorocholine (18F-choline) and gallium-68 prostate-specific membrane antigen (68Ga-PSMA) positron emission tomography (PET)-computed tomography (CT)–guided metastases-directed therapies (MDTs) in patients with castration-sensitive oligorecurrent prostate cancer (PC). Materials and Methods Inclusion criteria were: (1) histologically proven prostate adenocarcinoma; (2) evidence of biochemical relapse after primary tumor treatment; (3) ≤ 3 hypermetabolic oligorecurrent lesions detected by 18F-choline or 68Ga-PSMA PET-CT; (4) PET-CT imaging performed in a single nuclear medicine department; (5) patients treated with upfront stereotactic body radiotherapy (SBRT) without hormone therapy; and (6) SBRT delivered with a dose per fraction ≥ 5 Gy. In the case of oligoprogression (≤ 3 lesions outside the previous RT field) after MTD, a further course of SBRT was proposed; otherwise, androgen deprivation therapy (ADT) was administered. Results A total of 118 lesions in 88 patients were analyzed. Forty-four (50%) patients underwent 68Ga-PSMA PET-guided SBRT, and the remaining underwent choline PET-based SBRT. The median follow-up was 25 months (range, 5-87 months) for the entire cohort. Overall survival and local control were both 100%. Distant progression occurred in 48 (54.5%) patients, for a median distant progression-free survival of 22.8 months (range, 14.4-28.8 months). The median pre-SBRT prostate-specific antigen was 2.04 ng/mL in the choline PET cohort and 0.58 ng/mL in the PSMA-PET arm. Disease-free survival rates were 63.6% and 34%, respectively, in the 68Ga-PSMA and choline PET group (P = .06). The ADT administration rate was higher after choline-PET–guided SBRT (P = .00) owing to the higher incidence of polymetastatic disease after first-course SBRT compared with 68Ga-PSMA-based SBRT. Conclusion In the setting of oligorecurrent castration-sensitive PC, PSMA-PET-guided SBRT produced a higher rate of ADT-free patients when compared with the 18F-choline-PET cohort. Randomized trials are advocated.

"The hormone-naive oligometastatic prostate cancer is a challenging setting for the radiation oncology community, as it represents a sort of transition scenario potentially suitable for two different approaches: a local ablative treatment alone vs a metastasisdirected treatment with the addition of hormone therapy. The choice to add androgen deprivation therapy in the oligorecurrent hormone-sensitive patient is a matter of debate, given the detrimental impact on quality of life and the number of adverse events. To date, there is no clear agreement on the optimal management of this subset of patients. As some authors highlight the attractiveness of a local approach alone, as well tolerated, easily repeatible and with very limited costs, on the other hand, other authors focus the need to cover the micrometastatic disease, often not detectable, even with the newly available imaging modalities. In this commentary, we briefly summarize the literature data in support of both therapeutic strategies."

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.

Backround: Oral mucositis (OM) consists of a major side effect of radiotherapy (RT) in head and neck (H-N) cancer patients and natural honey is gaining more and more scientific interest due to its beneficial effects in tissue repair. Objective: The aim of this review is to better clarify the preventive/therapeutic role of honey in the management of OM in patients with H-N cancer undergoing RT with or without chemotherapy (CT). Methods: We used the PubMed database to retrieve journal articles and the inclusion criteria were only reviews and meta-analyses that illustrated the effective use of honey for either the prevention or treatment of OM in H-N cancer patients receiving either RT alone or in combination with CT. Results: Our search resulted in 92 citations, of which 12 eventually fulfilled the inclusion criteria of our study. Decreased incidence and severity of OM, extended time of occurrence of mucositis, less weight loss and less treatment interruptions were occasionally documented with conventional honey use in the included reviews and meta-analyses. In contrast to conventional honey, manuka honey proved to be weak in improving OM management in the small number of included reviews in our search. Conclusion: Conventional honey might constitute a highly promising natural product against OM attracting much scientific interest due to its easy accessibility and low financial cost. Hence, the lack of studies with high evidence requires further advanced research to enhance the existing knowledge about the potential value of honey in radiation-induced OM in H-N cancer patients.

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.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.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.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.

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. 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

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). 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. 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

Introduction: Radiotherapy is an important therapeutic strategy in the management of non-small cell lung cancer (NSCLC). In recent decades, technological implementations and the introduction of ima...

To evaluate tolerance and biochemical control rates of salvage external beam radiotherapy (EBRT) in patients with local relapse from prostate cancer (PC) after high-intensity focused ultrasound (HIFU) as primary treatment. Twenty-four patients presented biochemical failure of PC. Salvage EBRT to the residual prostate was performed with moderate hypofractionation schedule (MHRT) in 28 fractions (n = 16) or with extreme hypofractionation schedule (SBRT) in 5 fractions (n = 8) by means of image-guided volumetric modulation arc therapy. In case of MHRT, the median dose was 71.4 Gy, whereas in case of SBRT it was 32.5 Gy. The median follow-up was 28 months. The median PSA nadir was 0.26 ng/mL. In case of MHRT, the median PSA nadir was 0.15 ng/mL and occurred within a median time of 19 months. In case of SBRT, the median PSA nadir was 0.64 ng/mL and occurred within a median time of 8 months. No G3 higher acute or late toxicity after EBRT was observed. Only three patients presented with G2 acute GI toxicity (actinic proctitis). Twelve patients experienced acute G1 GU toxicity: 8/16 of men treated with MHRT and 4/8 of men treated with SBRT. Complete local control of disease was achieved in 23/24 patients (96%). Our data confirm the feasibility and the low toxicity of salvage EBRT with both schedules of treatment after HIFU failure. The findings of low acute toxicity and good biochemical control rates are encouraging, but a larger number of patients and a longer follow-up are needed to confirm these results.

Background/aim Medulloblastoma is a rare tumor of adult age, while it occurs more frequently in children. Given the rarity, there is a lack of evidence for the treatment of recurrent disease. Few data are available about salvage re-irradiation collecting very heterogeneous series. Case report A 51-year-old male presented with headache, nausea, double vision, and gait disorders. A contrast-enhanced brain-MRI showed the presence of multifocal medulloblastoma. After surgery, adjuvant craniospinal radiotherapy was performed, chemotherapy was stopped due to toxicity. After 27 months, a new MRI and a Methionine-PET revealed a late pontocerebellar relapse; multidisciplinary board decided for a SBRT treatment. The second course of RT was well tolerated and 14 months later, the patient is alive in good general conditions, with no evidence of disease. Conclusion Our experience supports the use of salvage stereotactic radiotherapy as a safe and effective treatment option.

Cutaneous sarcomas are a heterogeneous group of rare mesenchymal neoplasms representing less than 1% of malignant tumors. Histology report remains the cornerstone for the diagnosis of these tumors. The most important clinicopathologic parameters related to prognosis include larger tumor size, high mitotic index, head and neck location, p53 mutations, depth of infiltration and histological grade, vascular and perineural invasion as well as the surgical margins status. Applying advanced biopsy techniques might offer more precise assessment of surgical margins, which constitutes a significant precondition for the management of these tumors. The management of cutaneous soft tissue sarcomas requires a multidisciplinary approach. Surgery remains the standard treatment, nonetheless adjuvant therapy may be required, consisting of radiotherapy, chemotherapy, and molecular targeted therapies to improve treatment outcomes. The role of molecular profiling in the treatment of uncontrolled disease is promising, but it may be offered to a relatively small proportion of patients and its use is still considered experimental in this setting. Due to the rarity of the disease, there is a need for knowledge and experience to be shared, pooled, organized and rationalized so that recent developments in medical science can have a major impact on the disease course. Multicenter clinical trials are needed to improve the care of patients with cutaneous sarcomas. info:eu-repo/semantics/publishedVersion

Introduction: The aim of our study was to evaluate the efficacy and toxicity of a daily adaptive MR-guided SBRT on 1.5 T MR-linac in patients affected by lymph node oligometastases from PCa. Materials and Methods: The present study is a prospective observational study conducted in a single institution (protocol n°: MRI/LINAC n. 23748). Patients with oligometastatic lymph nodes from PCa treated with daily adaptive MR-guided SBRT on 1.5 T MR-linac were included in the study. There was a minimum required follow-up of 3 months after SBRT. The primary end-point was local progression-free survival (LPFS). The secondary end-points were: nodal progression-free survival (NPFS), progression-free survival (PFS), and toxicity. Results: A total of 118 lymph node oligometastases from PCa were treated with daily adaptive 1.5 T MR-guided SBRT in 63 oligometastatic patients. Of the patients, 63.5% were oligorecurrent and 36.5% were oligoprogressive. The two-year LPFS was 90.7%. The median NPFS was 22.3 months and the 2-year NPFS was 46.5%. Receiving hormone therapy before SBRT was correlated with a lower NPFS at the multivariate analysis (1 y NPFS 87.1% versus 42.8%; p = 0.002–HR 0.199, 95% CI 0.073–0.549). Furthermore, the oligorecurrent state during ADT was correlated with a lower NPFS than was the oligoprogressive state. The median PFS was 10.3 months and the 2-year PFS was 32.4%. Patients treated with hormone therapy before SBRT had a significantly lower 1-year PFS the others (28% versus 70.4%; p = 0.01–HR 0.259, 95% CI 0.117–0.574). No acute and late toxicities occurred during treatment. Conclusions: The present study is the largest prospective study of 1.5 T lymph node SBRT on MR-linac in patients with PCa. Lymph node SBRT by 1.5 T MR-linac provides high local control rates with an excellent toxicity profile.

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.

Breast cancer is a heterogenous disease with a deep tailoring level. Evidence is accumulating on the role of stereotactic body radiotherapy (SBRT) in the management of oligometastatic disease, however this is limited in breast cancer. The aim of the present study is to show the effectiveness of SBRT in delaying the switch to a subsequent systemic treatment in oligoprogressive breast cancer patients. Retrospective analysis from two Institutions. Primary endpoint: time to next systemic treatment (NEST). Secondary endpoints: freedom from local progression (FLP), time to the polymetastatic conversion (tPMC) and overall survival (OS). One-hundred fifty-three (153) metastases in 79 oligoprogressive breast cancer patients were treated with SBRT. Median follow-up 24 months. Median NEST 8 months. Predictive factor of NEST at the multivariate analysis (MVA) was the number of treated oligometastases (HR 1.765, 95%CI 1.322-2.355; p =0.01). Systemic treatment after SBRT was changed in 29 patients for polymetastatic progression and in 10 patients for oligometastatic progression6 months after SBRT. The 2-year FLP in the overall population was 86.7%. A biological effective dose (BED)70Gy

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.

Hybrid magnetic resonance (MR)-guided linear accelerators represent a new horizon in the field of radiation oncology. By harnessing the favorable combination of on-board MR-imaging with the possibility to daily recalculate the treatment plan based on real-time anatomy, the accuracy in target and organs-at-risk identification is expected to be improved, with the aim to provide the best tailored treatment. To date, two main MR-linac hybrid machines are available, Elekta Unity and Viewray MRIdian. Of note, compared to conventional linacs, these devices raise practical issues due to the positioning phase for the need to include the coil in the immobilization procedure and in order to perform the best reproducible positioning, also in light of the potentially longer treatment time. Given the relative novelty of this technology, there are few literature data regarding the procedures and the workflows for patient positioning and immobilization for MR-guided daily adaptive radiotherapy. In the present narrative review, we resume the currently available literature and provide an overview of the positioning and setup procedures for all the anatomical districts for hybrid MR-linac systems. Supplementary Information The online version contains supplementary material available at 10.1186/s13014-021-01910-6.

BackgroundThe 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. MethodsRadiotherapy 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. ResultsA 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-years overall survival rates were both 70%. No acute or late G≥2 adverse events were observed.ConclusionsIn 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, highilighting the effectiveness of this therapeutic option. Prospective studies to further explore this approach in this setting are advocated.

Adrenal metastases occur in 15–35% of oncological patients. Surgery is the first treatment option. Stereotactic body radiotherapy (SBRT) has been largely explored in oligometastatic patients unfit for surgery, representing an effective and non-invasive local treatment. The results of a multi-institutional experience of SBRT on adrenal metastases in the oligorecurrent or oligoprogressive setting are herein reported. We collected data of adrenal gland metastases treated with SBRT in three Italian centers from 2010 to 2020. End-points of the present study were: Overall survival (OS), Local control of treated metastases (LC), Progression free survival (PFS), and toxicity. 149 adrenal gland metastases were treated with SBRT in 142 patients. The most common primary tumor was lung cancer (58.4%), followed by kidney cancer (9.4%). Median lesion’s volume was 28.5 cm3 (2.5–323.4). The median SBRT dose was 40 Gy (10–60). Median follow-up was 14.4 months. One- and two-year OS were 72.3% and 53.5%. At univariate analysis performance status correlated with survival (HR 1.57, p = 0.006). One- and two-year LC were 85.4% and 79.2%, with lung primary tumor (HR 0.33, p = 0.021) and BED10 (HR 0.97, p = 0.036) significant independent factors. One- and two-year PFS were 37.7% and 24.8%. Median time to polymetastatic disease was 11.3 months. Grade 1 and 2 toxicity occurred in 21 (14.7%) and 3 (2.1%) patients. The results from this large multi-center study confirm the efficacy and safety of SBRT in the management of adrenal gland metastases, as a valid alternative to other more invasive local approaches.

PURPOSE Given the absence of standardized planning approach for clinically node-positive (cN1) prostate cancer (PCa), we collected data about the use of prophylactic pelvic irradiation and nodal boost. The aim of the present series is to retrospectively assess clinical outcomes after this approach to compare different multimodal treatment strategies in this scenario. METHODS Data from clinical records of patients affected by cN1 PCa and treated in six different Italian institutes with prophylactic pelvic irradiation and boost on pathologic pelvic lymph nodes detected with CT, MRI or choline PET/CT were retrospectively reviewed and collected. Clinical outcomes in terms of overall survival (OS) and biochemical relapse-free survival (b-RFS) were explored. The correlation between outcomes and baseline features (International Society of Urological Pathology-ISUP pattern, total dose to positive pelvic nodes ≤ / > 60 Gy, sequential or simultaneous integrated boost (SIB) administration and definitive vs postoperative treatment) was explored. RESULTS ISUP pattern

Aims: To assess toxicity and clinical outcomes of moderately hypofractionated helical tomotherapy (HT) for the curative treatment of localized prostate cancer (PC). Methods: From December 2012 to May 2018, 170 patients were treated with definitive intent for PC. Thirty-four percent were low risk, 30% intermediate risk (IR) and 36% high risk (HR). All patients received 70Gy in 28 fractions to the prostate; 61.6Gy were delivered to the seminal vesicles for IR; pelvic lymph nodes irradiation for a total dose of 50.4Gy was added in the HR subgroup. Toxicity was assessed using CTCAE V4.0, and biochemical failure was defined following Phoenix criteria. Time-to-event data were analyzed using the Kaplan–Meier method and log-rank test. Results: The median follow-up was 36months (range 12–78); acute toxicity was as follows: G1 and G2 in 27.6% and 19.4% for GI; 53% and 24% for GU. No G ≥ 3 event was observed. For late toxicity, G ≥ 3 GI and GU rates were, respectively, 3% and 2.4% at 3years and 3% and 4.8% at 4years; no G4 occurred. A statistical correlation between acute or late G3 incidence and clinical or dosimetric parameters was not found. At the time of analysis, 2- and 3-year biochemical relapse-free survival rates were 90% and 87.5% and 2- and 3-year overall survival rates were 96.4% and 90%, respectively. The log-rank test revealed no difference between the risk groups in terms of biochemical control (p = 0.16). Conclusions: Moderately hypofractionated RT with HT for localized prostate cancer reported excellent outcomes with mild acute and late toxicity incidence, with promising biochemical control rates.

PurposeWe 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. MethodsA 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 35Gy in 5 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-valueResultsAverage baseline PTV, bowel, bladder and single intestinal loop volumes were respectively 8.9cc (range, 0.7-41.2cc), 1176cc (119-3654 cc), 95cc (39.7-202.9 cc), 18.3cc (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].ConclusionsDaily-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.

Simple Summary The biological features of prostate cancer as a tumor with a low alpha beta ratio have led clinicians to consider the use of higher doses per fraction, thus gaining an advantage both in terms of clinical outcomes and of logistic opportunities. To date, moderate hypofractionated schedules are supported by several international clinical guidelines. The subsequent step was represented by the adoption of extreme hypofractionated schedules, for which recent literature data report non-inferiority results for the five-fractions regimens. In this scenario, the recent introduction of MR-guided daily adaptive radiotherapy is a potential paradigm shift, given the ability to increase the resolution of the pelvis anatomy and to take into account of the daily variations in shape and size of the nearby healthy structures. Abstract In this review we summarize the currently available evidence about the role of hybrid machines for MR-guided radiotherapy for prostate stereotactic body radiotherapy. Given the novelty of this technology, to date few data are accessible, but they all report very promising results in terms of tolerability and preliminary clinical outcomes. Most of the studies highlight the favorable impact of on-board magnetic resonance imaging as a means to improve target and organs at risk identification with a consequent advantage in terms of dosimetric results, which is expected to relate to a more favorable toxicity pattern. Still, the longer treatment time per session may potentially affect the patient’s compliance to the treatment, although first quality of life assessment studies have reported substantial tolerability and no major impact on quality of life. Finally, in this review we hypothesize some future scenarios of further investigation, based on the possibility to explore the superior anatomy visualization and the role of daily adapted treatments provided by hybrid MR-Linacs.

To report preliminary data on feasibility and patient-reported outcomes following PSMA-PET/CT guided SBRT by means of 1.5 T MRI-Linac. 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. 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. 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.

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 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.

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.

Radiosurgery (SRS) is an effective treatment option for brain metastases (BMs). Long-term results of the first worldwide experience with a mono-isocentric, non-coplanar, linac-based stereotactic technique in the treatment of multiple BMs are reported. patients with multiple BMs, life expectancy > 3 months, and good performance status (≤ 2) were treated with simultaneous SRS with volumetric modulated arc technique. Data were retrospectively evaluated. 172 patients accounting for 1079 BMs were treated at our institution from 2017 to 2020. The median number of treated metastases was 4 (range 2–22). Primary tumor histology was: lung (44.8%), breast (32%), and melanoma (9.4%). The 2-year LPFS was 71.6%, respectively. A biological effective dose (BED) ≥ 51.3 Gy10 correlated with higher local control. Uncontrolled systemic disease and melanoma histology were independent prognostic factors correlated with decreased iPFS. Patients with > 10 BMs had a trend towards shorter iPFS (p = 0.055). 31 patients received multiple SRS courses (2–7) in case of intracranial progression. The median iOS was 22.4 months. Brainstem metastases and total PTV > 7.1 cc correlated with shorter iOS. The 1- and 2-year WBRT-free survival was 83.2% and 61.1%, respectively. Long-term results in a large patient population treated with a mono-isocentric, dedicated technique demonstrated its effectiveness and safety also in the case of multiple courses. The shortened treatment time and the possibility to safely spare healthy brain tissue allows the safe treatment of patients with a large number of metastases and to deliver multiple courses of SRS. In selected cases, the administration of WBRT can be delayed.