ONE SHOT - single shot radiotherapy for localized prostate cancer: 18-month results of a single arm, multicenter phase I/II trial.

PURPOSE: To assess in a prospective, multicenter, single-arm phase I/II study the early safety and efficacy profile of single fraction urethra-sparing stereotactic body radiotherapy (SBRT) for men with localized prostate cancer. MATERIAL AND METHODS: Patients with low- and intermediate-risk localized prostate cancer without significant tumor in the transitional zone were recruited. A single-fraction of 19 Gy was delivered to the prostate, with 17 Gy dose-reduction to the urethra. Intrafraction motion was monitored using intraprostatic electromagnetic transponders with intra-fraction correction of displacements exceeding 3 mm. Genitourinary (GU), gastrointestinal (GI), and sexual toxicity during the first 18 months were evaluated using the CTCAE v4.0 grading scale. Quality of life was assessed using the International Prostate Symptom Score, the Expanded Prostate Cancer Index composite 26 score, and the International Index of Erectile Function score. RESULTS: Among the 45 patients recruited in 5 centers between 2017 and 2022, 43 received the single fraction without protocol deviations, and 34 had a minimal follow-up of 18 months. The worst GU toxicity was observed at day-5 after SBRT (42.5 % and 20 % with grade 1 and 2, respectively), returning to baseline at week-12 and month-6 (<3% with grade 2), with a 12 % grade 2 flare at month 18. Gl toxicity was mild in the acute phase, with no grade ≥ 2 events (12 % grade 1 at month 6). Grade-3 proctitis was observed in one patient at month 12, with < 3 % grade 2 toxicity at month 18. Mean GU and GI bother scores showed a decline at day 5, a complete recovery at month 6, and a flare between month 12 and 18. Mean PSA dropped from 6.2 ng/ml to 1.2 ng/ml at month 18 and 0.7 ng/ml at month 24. After a median follow-up time of 26 months, 3 biochemical failures (7 %) were observed at month 17, 21 and 30. CONCLUSIONS: In this multicenter phase I/II trial, we demonstrated that a 19 Gy single-fraction urethra-sparing SBRT is feasible and associated with an acceptable toxicity rate, mostly returning to the baseline at week-12 and with a symptoms flare between months 12 and 18. Longer follow-up is needed to assess the potential long-term adverse effects and the disease control efficacy.

Sterotactic Ablative Radiotherapy in a Multicentric Series of Oligometastatic SCLC: The SAMOS Cohort.

AIMS: SCLC is the most aggressive lung cancer histology with a 5-year OS <10%. At the diagnosis, almost two-thirds of the SCLC an Extended Disease presentation. Two randomized studies (CASPIAN and ImPower133) demonstrated an OS improvement, when immunotherapy was prescribed as maintenance therapy after standard chemotherapy. To date, SABR has had a limited indication in managing metastatic SCLC, although recent reports proposed it as a valid treatment option in selected patients. We propose a retrospective multicentric analysis of patients treated with SABR for oligometastatic SCLC. METHOD: Data of patients affected by oligometastatic-SCLC treated with SABR between 2017 and 2022 in 11 Italian centers were collected. Clinical and therapeutic variables together with OS and time to next treatment were analyzed. Univariate analysis with Kaplan-Meier curve were calculated, and log-rank test were applied. Cox proportional hazard model was used for multivariate analysis. RESULTS: Data from 93 patients and 132 metastatic lesions were analyzed. The median age was 64 years (36-86) and all but 1 had Performance Status 0 or 1. Fifty-two patients presented ED at diagnosis. The first line treatment was radiochemotherapy in 42%, CHT alone in 24% and CHT-IO in 28%, others treatment accounts for 4% and only 2% of patients underwent best supportive care. Of the 132 lesions treated with SBRT 55 were in brain, 27 in lung, 11 in liver, 10 in lymph nodes, 8 in bones and 20 in adrenal gland. Median OS was 14 months, 1 year-OS and 2 years OS were 53% and 27%, respectively. The median TtNT was 14 months for the entire population. Of all the analyzed variables only, the anatomical site of the metastases and their number showed statistical significance in the univariate analysist, confirmed in the subsequent multivariate. CONCLUSION: SABR seems to play a role in delaying further systemic lines in oligometastatic disease and to extend the use of ongoing treatment in oligoprogressive state. Prospective studies are needed to confirm these findings.

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.

Refining critical structure contouring in STereotactic Arrhythmia Radioablation (STAR): Benchmark results and consensus guidelines from the STOPSTORM.eu consortium.

BACKGROUND AND PURPOSE: In patients with recurrent ventricular tachycardia (VT), STereotactic Arrhythmia Radioablation (STAR) shows promising results. The STOPSTORM.eu consortium was established to investigate and harmonise STAR treatment in Europe. The primary goals of this benchmark study were to standardise contouring of organs at risk (OAR) for STAR, including detailed substructures of the heart, and accredit each participating centre. MATERIALS AND METHODS: Centres within the STOPSTORM.eu consortium were asked to delineate 31 OAR in three STAR cases. Delineation was reviewed by the consortium expert panel and after a dedicated workshop feedback and accreditation was provided to all participants. Further quantitative analysis was performed by calculating DICE similarity coefficients (DSC), median distance to agreement (MDA), and 95th percentile distance to agreement (HD95). RESULTS: Twenty centres participated in this study. Based on DSC, MDA and HD95, the delineations of well-known OAR in radiotherapy were similar, such as lungs (median DSC = 0.96, median MDA = 0.1 mm and median HD95 = 1.1 mm) and aorta (median DSC = 0.90, median MDA = 0.1 mm and median HD95 = 1.5 mm). Some centres did not include the gastro-oesophageal junction, leading to differences in stomach and oesophagus delineations. For cardiac substructures, such as chambers (median DSC = 0.83, median MDA = 0.2 mm and median HD95 = 0.5 mm), valves (median DSC = 0.16, median MDA = 4.6 mm and median HD95 = 16.0 mm), coronary arteries (median DSC = 0.4, median MDA = 0.7 mm and median HD95 = 8.3 mm) and the sinoatrial and atrioventricular nodes (median DSC = 0.29, median MDA = 4.4 mm and median HD95 = 11.4 mm), deviations between centres occurred more frequently. After the dedicated workshop all centres were accredited and contouring consensus guidelines for STAR were established. CONCLUSION: This STOPSTORM multi-centre critical structure contouring benchmark study showed high agreement for standard radiotherapy OAR. However, for cardiac substructures larger disagreement in contouring occurred, which may have significant impact on STAR treatment planning and dosimetry evaluation. To standardize OAR contouring, consensus guidelines for critical structure contouring in STAR were established.

Activity of sotorasib against brain metastases from NSCLC harboring KRAS p.G12C mutation: a case report.

In the CodeBreaK 100 phase 2 study, sotorasib was active for patients with metastatic non-small cell lung cancer (NSCLC) harboring Kirsten rat sarcoma viral oncogene homologue (KRAS) p.G12C mutation. However, patients with untreated and/or active brain metastases were excluded from the trial, and the activity of sotorasib in the setting of brain metastases should be further investigated. Here we report the case of a KRAS p.G12C mutant NSCLC patient with three brain metastases, of whom one was untreated and the other two had progressed after radiotherapy with symptoms requiring steroids, that responded to sotorasib. Our report suggests that sotorasib may be active against untreated or progressive brain metastases, supporting further evaluation of sotorasib in this setting.

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.

Technological advancements and future perspectives in breast cancer radiation therapy.

INTRODUCTION: Breast cancer is still one of the most common tumors worldwide and radiation therapy has a central role in the oncological pathway. Several technological options are now available with the aim to improve therapeutic index, target definition, and patient selection. AREAS COVERED: In this review, we summarize current available technologies in the management of breast cancer. These advances can support the prescription of postoperative partial breast cancer treatment and preoperative stereotactic partial breast irradiation. Moreover, image-guided radiotherapy is crucial for high-quality radiation treatments. Additionally, the recent development of hybrid magnetic resonance linear accelerator can impact target volume outline procedure, adaptive planning and radiomics. Finally, artificial intelligence represents the new frontier in medicine, supporting clinicians in target definition, patient selection, and treatment planning. EXPERT OPINION: In patients with breast cancer the overall level of evidence about new technologies is still low even if some advances are potentially very interesting to further development.

Systemic treatment and radiotherapy for patients with non-small cell lung cancer (NSCLC) and HIV infection - A systematic review.

Lung cancer is the most common non-AIDS defining cancer among people living with HIV (PLWH), but there is a paucity of data regarding the efficacy and toxicity of radiotherapy and systemic regimens, including immunotherapy, in the treatment of these patients. In order to answer this question, we have performed a systematic search of the literature in Ovid Medline until March 17, 2022. We included 21 publications, enrolling 513 PLWH with non-small cell lung cancer (NSCLC), mostly male (75-100%), (ex-)smokers (75-100%) and with stage III-IV at diagnosis (65-100%). The overall response rate (ORR) to chemotherapy (n = 186 patients, mostly receiving platinum-based regimens) was highly variable (17 %-83 %), with a substantial hematological toxicity. ORR varied between 13 % and 50 % with single-agent immunotherapy (n = 68), with median overall survival between 9 and 11 months and a very acceptable toxicity profile, in line with studies in the HIV non-infected population. All five patients receiving tyrosine kinase inhibitors (TKIs; gefitinib or erlotinib) showed a partial response and long overall survival. Yet, combination of TKIs with antiretroviral therapy using pharmacological boosters, such as ritonavir, should be avoided. Radiotherapy was evaluated among 42 patients, showing high ORR (55 %-100 %), but 18 % of patients had a pneumonitis. This systematic review shows that radiotherapy and systemic therapy are effective and safe among PLWH with controlled infection diagnosed with NSCLC. Nonetheless, most reports were small and heterogeneous and larger studies are needed to confirm these encouraging findings. Moreover, clinical trials should not restrict the inclusion of PLWH, as more data is needed regarding the long-term efficacy and safety of treatments among this underserved population, especially of immunotherapy.

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.

1.5 T MR-Guided Daily Adapted SBRT on Lymph Node Oligometastases from Prostate Cancer.

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.

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

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

Stereotactic radiosurgery for the treatment of brainstem metastases: a multicenter retrospective study.

BACKGROUND: Brainstem metastases (BSM) are associated with a poor prognosis and their management represents a therapeutic challenge. BSM are often inoperable and, in absence of randomized trials, the optimal radiation treatment of BSM remains to be defined. We evaluated the efficacy and toxicity of linear accelerator (linac)-based stereotactic radiosurgery (SRS) and hypofractionated steretotactic radiotherapy (HSRT) in the treatment of BSM in a series of patients treated in different clinical centers. METHODS: We conducted a multicentric retrospective study of patients affected by 1-2 BSM from different histologies who underwent SRS/HSRT. Freedom from local progression (FLP), cancer-specific survival (CSS), overall survival (OS), and treatment-related toxicity were evaluated. In addition, predictors of treatment response and survivals were evaluated. RESULTS: Between 2008 and 2021, 105 consecutive patients with 111 BMS who received SRS or HSRT for 1-2 BSM were evaluated. Median follow-up time was 10 months (range 3-130). One-year FLP rate was 90.4%. At the univariate analysis, tumor volume ≤ 0.4 cc, and concurrent targeted therapy were associated with longer FLP, with combined treatment that remained a significant independent predictor [0.058, HR 0.139 (95% CI 0.0182-1.064]. Median OS and CSS were 11 months and 14.6 months, respectively. At multivariate analysis, concurrent targeted therapy administration was significantly associated with longer OS [HR 0.514 (95%CI 0.302-0.875); p = 0.01]. Neurological death occurred in 30.4% of patients, although this was due to local progression in only 3 (2.8%) patients. CONCLUSION: Linac-based SRS/HSRT offers excellent local control to patients with BSM, with low treatment-related toxicity and no apparent detrimental effects on OS. When treated with ablative intent, BSM are an uncommon cause of neurological death. The present results indicates that patients with BSM should not be excluded a priori from clinical trials.

Novel Harmonization Method for Multi-Centric Radiomic Studies in Non-Small Cell Lung Cancer.

The purpose of this multi-centric work was to investigate the relationship between radiomic features extracted from pre-treatment computed tomography (CT), positron emission tomography (PET) imaging, and clinical outcomes for stereotactic body radiation therapy (SBRT) in early-stage non-small cell lung cancer (NSCLC). One-hundred and seventeen patients who received SBRT for early-stage NSCLC were retrospectively identified from seven Italian centers. The tumor was identified on pre-treatment free-breathing CT and PET images, from which we extracted 3004 quantitative radiomic features. The primary outcome was 24-month progression-free-survival (PFS) based on cancer recurrence (local/non-local) following SBRT. A harmonization technique was proposed for CT features considering lesion and contralateral healthy lung tissues using the LASSO algorithm as a feature selector. Models with harmonized CT features (B models) demonstrated better performances compared to the ones using only original CT features (C models). A linear support vector machine (SVM) with harmonized CT and PET features (A1 model) showed an area under the curve (AUC) of 0.77 (0.63-0.85) for predicting the primary outcome in an external validation cohort. The addition of clinical features did not enhance the model performance. This study provided the basis for validating our novel CT data harmonization strategy, involving delta radiomics. The harmonized radiomic models demonstrated the capability to properly predict patient prognosis.

Stereotactic ablative radiotherapy in patients with refractory ventricular tachyarrhythmia.

Stereotactic ablative body radiotherapy (SABR) is an innovative therapeutic approach in patients (pts) with a diagnosis of refractory ventricular tachyarrhythmia (VT) after the use of drugs, radiofrequency catheter ablation, and/or defibrillator (ICD) implant. The current efficacy data of SABR are limited and several prospective clinical studies are ongoing to support the use of ablative radiation dose to control VT. The aim of the current prospective pilot study is to report the efficacy and tolerability of SABR in ICD implanted pts with refractory VT in our centre. Non-invasive electroanatomical mapping (EAM), cardiac computed tomography (CT), and 18F-fluorodeoxyglucose positron emission (FDG-PET)-CT scan were used and combined with a radiation CT scan. A dose prescription of 25 Gy in a single dose was delivered by volumetric modulated arc therapy (VMAT) Linac-based. The primary endpoint was efficacy, defined as a reduction in ICD shocks after SABR treatment, while the secondary endpoint was safety. Six consecutive pts (five males and one female) implanted with an ICD and with three or more VT were enrolled. One pts died after 1 month, due to end-stage heart failure. Two pts experienced ICD shocks in VT 2 and 5 months after treatment. Three pts experienced no more ICD shocks on VT after therapy. Our data suggest the efficacy and safety of SABR treatment in pts with VT. Larger dataset of pts and longer follow-up are otherwise required to validate the impact of SABR as a standardized treatment in these pts.

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.

Immunotherapy in NSCLC Patients With Brain and Leptomeningeal Metastases.

Immunotherapy has now been integrated as a treatment strategy for most patients with non-small cell lung cancer (NSCLC). However, the pivotal clinical trials that demonstrated its impressive efficacy often did not include patients with active, untreated brain metastases or leptomeningeal carcinomatosis. Nevertheless, NSCLC is the most common tumor to metastasize to the brain, and patients develop brain and meningeal involvement in approximately 40 and 10% of cases, respectively. Consequently, the appropriate care of these patients is a recurrent clinical concern. Although there are many aspects that would merit further investigation to explain the mechanism of intracranial response to immune checkpoint inhibitors (ICPs), some data suggest that they are able to cross the blood-brain barrier, resulting in local tumor microenvironment modification. This results in a similar clinical benefit in patients with stable, previously treated brain metastases compared to the general population. Despite important limitations, some real-life studies have described that the ICPs' efficacy was maintained also in less selected patients with untreated or symptomatic brain metastases. In contrast, few data are available about patients with leptomeningeal carcinomatosis. Nevertheless, neurological complications due to ICP treatment in patients with brain metastases have to be evaluated and carefully monitored. Despite the fact that limited data are available in the literature, the purpose of this review is to show that the multimodal treatment of these patients with brain metastases and/or leptomeningeal disease should be discussed during tracing of the history of the disease, participating in the local and possibly systemic control of NSCLC.

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.

Stereotactic body radiotherapy (SBRT) and concomitant systemic therapy in oligoprogressive breast cancer patients.

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 progression < 6 months after SBRT. The 2-year FLP in the overall population was 86.7%. A biological effective dose (BED) > 70Gy10 was associated with improved FLP (90% versus 74.2%). The median tPMC was 10 months. At the MVA the only factors significantly associated with tPMC were the number of oligometastases (HR 1.172, 95%CI 1.000-1.368; p = 0.03), and the local control of the treated metastases (HR 2.726, CI95% 1.108-6.706; p = 0.02). SBRT can delay the switch to a subsequent systemic treatment, however patient selection is necessary. Several predictive factors for treatment tailoring have been identified.

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

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