Efficacy of stereotactic body radiotherapy and response prediction using artificial intelligence in oligometastatic gynaecologic cancer.

PURPOSE: We present a large real-world multicentric dataset of ovarian, uterine and cervical oligometastatic lesions treated with SBRT exploring efficacy and clinical outcomes. In addition, an exploratory machine learning analysis was performed. METHODS: A pooled analysis of gynecological oligometastases in terms of efficacy and clinical outcomes as well an exploratory machine learning model to predict the CR to SBRT were carried out. The CR rate following radiotherapy (RT) was the study main endpoint. The secondary endpoints included the 2-year actuarial LC, DMFS, PFS, and OS. RESULTS: 501 patients from 21 radiation oncology institutions with 846 gynecological metastases were analyzed, mainly ovarian (53.1%) and uterine metastases(32.1%).Multiple fraction radiotherapy was used in 762 metastases(90.1%).The most frequent schedule was 24 Gy in 3 fractions(13.4%). CR was observed in 538(63.7%) lesions. The Machine learning analysis showed a poor ability to find covariates strong enough to predict CR in the whole series. Analyzing them separately, in uterine cancer, if RT dose≥78.3Gy, the CR probability was 75.4%; if volume was <13.7 cc, the CR probability became 85.1%. In ovarian cancer, if the lesion was a lymph node, the CR probability was 71.4%; if volume was <17 cc, the CR probability rose to 78.4%. No covariate predicted the CR for cervical lesions. The overall 2-year actuarial LC was 79.2%, however it was 91.5% for CR and 52.5% for not CR lesions(p < 0.001). The overall 2-year DMFS, PFS and OS rate were 27.3%, 24.8% and 71.0%, with significant differences between CR and not CR. CONCLUSIONS: CR was substantially associated to patient outcomes in our series of gynecological cancer oligometastatic lesions. The ability to predict a CR through artificial intelligence could also drive treatment choices in the context of personalized oncology.

Stereotactic MR-guided adaptive radiotherapy (SMART) for primary rectal cancer: evaluation of early toxicity and pathological response.

Background: The purpose of this study is to measure the effects of stereotactic MR-guided adaptive radiotherapy (SMART) for rectal cancer patients in terms of early toxicity and pathological response. Materials and methods: For this prospective pilot study, patients diagnosed with locally advanced rectal cancer (LARC) with positive lymph node clinical staging underwent SMART on rectal lesion and mesorectum using hybrid MR-Linac (MRIdian ViewRay). Dose prescription at 80% isodose for the rectal lesion and mesorectum was 40 Gy (8 Gy/fr) and 25 Gy (5 Gy/fr), respectively, delivered on 5 days (3 fr/week). Response assessment by MRI was performed 3 weeks after SMART, then patients fit for surgery underwent total mesorectal excision. Primary endpoint was evaluation of adverse effect of radiotherapy. Secondary endpoint was pathological complete response rate. Early toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Results: From October 2020 to January 2022, twenty patients underwent rectal SMART. No grade 3-5 toxicity was recorded. Twelve patients were eligible for total mesorectal excision (TME). Mean interval between the completion of SMART and surgery was 4 weeks. Pathological downstaging occurred in all patients; rate of pathological complete response (pCR) was 17%. pCR occurred with a prolonged time to surgery (> 7 weeks). Conclusion: To our knowledge, this is the first study to use stereotactic radiotherapy for primary rectal cancer. SMART for rectal cancer is well tolerated and effective in terms of tumor regression, especially if followed by delayed surgery.

Magnetic resonance guided SBRT reirradiation in locally recurrent prostate cancer: a multicentric retrospective analysis.

AIMS: Reirradiation of prostate cancer (PC) local recurrences represents an emerging challenge for current radiotherapy. In this context, stereotactic body radiation therapy (SBRT) allows the delivery of high doses, with curative intent. Magnetic Resonance guided Radiation Therapy (MRgRT) has shown promising results in terms of safety, feasibility and efficacy of delivering SBRT thanks to the enhanced soft tissue contrast and the online adaptive workflow. This multicentric retrospective analysis evaluates the feasibility and efficacy of PC reirradiation, using a 0.35 T hybrid MR delivery unit. METHODS: Patients affected by local recurrences of PC and treated in five institutions between 2019 and 2022 were retrospectively collected. All patients had undergone previous Radiation Therapy (RT) in definitive or adjuvant setting. Re-treatment MRgSBRT was delivered with a total dose ranging from 25 to 40 Gy in 5 fractions. Toxicity according to CTCAE v 5.0 and treatment response were assessed at the end of the treatment and at follow-up. RESULTS: Eighteen patients were included in this analysis. All patients had previously undergone external beam radiation therapy (EBRT) up to a total dose of 59.36 to 80 Gy. Median cumulative biologically effective dose (BED) of SBRT re-treatment was 213,3 Gy (103,1-560), considering an α/ß of 1.5. Complete response was achieved in 4 patients (22.2%). No grade ≥ 2 acute genitourinary (GU) toxicity events were recorded, while gastrointestinal (GI) acute toxicity events occurred in 4 patients (22.2%). CONCLUSION: The low rates of acute toxicity of this experience encourages considering MRgSBRT a feasibile therapeutic approach for the treatment of clinically relapsed PC. Accurate gating of target volumes, the online adaptive planning workflow and the high definition of MRI treatment images allow delivering high doses to the PTV while efficiently sparing organs at risk (OARs).

Clinical Outcomes and Toxicity of CT-guided High Dose-rate Brachytherapy in Women With Locally-advanced Cervical Cancer.

BACKGROUND/AIM: To evaluate the outcome and toxicities in patients with locally advanced cervical cancer (LACC) treated with radiochemotherapy and intracavitary brachytherapy. PATIENTS AND METHODS: This study included 67 patients with LACC treated between 2010 and 2018. The most represented stage was FIGO IIB. The patients were treated with external beam radiotherapy (EBRT) to the pelvis and boost to the cervix and parametrials. Concomitant chemotherapy (CHT) with cisplatin (CDDP) 40 mg/mq was planned. Subsequently, the patients underwent CT-based endouterine brachytherapy (BT). The response was evaluated at 3 months with PET-CT and/or pelvic magnetic resonance imaging (MRI). Since then, the patients have been followed with clinical instrumental controls every 4 months for the first 2 years and every 6 months for the following 3 years. Local response was assessed with pelvic MRI and/or PET-CT scan at the end of intracavitary BT) according to RECIST 1.1 criteria. RESULTS: The median duration of treatment was 55 days (range=40-73 days). The prescription dose to the planning target volume (PTV) was delivered in 25 to 30 (median 28) daily fractions. The EBRT median dose to the pelvis and gross tumor volume were 50.4 Gy (range=45-56.25) and 61.6 Gy (range=45-70.4), respectively. The 1-year, 2-year, 3-year, and 5-year overall survival rates were 92.44%, 80.81%, 78.84%, and 76.45% respectively. The actuarial 1-year, 2-year, 3-year, and 5-year disease-free survival rates were 89.5%, 83.6%, 81%, and 78.2% respectively. CONCLUSION: This study analyzed acute and chronic toxicity, survival, and local control in cervical cancer patients treated with IMRT followed by CT-planned high dose rate-brachytherapy. Patients demonstrated satisfactory outcomes and incidence of acute and late toxicities.

Feasibility of clinical target volume reduction for glioblastoma treated with standard chemoradiation based on patterns of failure analysis.

PURPOSE: To analyze recurrence patterns in patients with glioblastoma (GBM) after standard chemoradiation according to different target volume delineation strategies. METHODS AND MATERIALS: Two hundred seven patients with GBM who recurred after standard chemoradiation were evaluated. According to ESTRO target volume delineation guideline, the CTV was generated by adding a 2-cm margin to the GTV, defined as the resection cavity plus residual tumor. Patterns of failure were analyzed using dose-volume histogram. Recurrent lesions were defined as in-field, marginal, or distant if > 80 %, 20-80 %, or < 20 % of the intersecting volume was included in the 95 % isodose line.For each patient, a theoretical plan consisting of reduced 1-cm GTV-to-CTV margin was created to compare patterns of failure and radiation doses to normal brain. RESULTS: Median overall survival and progression-free survival times were 15.3 months and 7.8 months, respectively, from the date of surgery. Recurrences were in-field in 180, marginal in 5, and distant in 22 patients. According to MGMT promoter methylation, distant recurrences occurred in 18.6 % of methylated and 6 % of unmethylated tumors (p = 0.0046). Following replanning with 1-cm reduced margin, dosimetric analysis showed similar patterns of failure. Recurrences were in-field, marginal, and distant in 177, 3, and 27 plans, respectively, although radiation doses to the healthy brain and hippocampi were significantly lower compared with standard target delineation (p = 0.0001). CONCLUSION: Current provide the rationale for evaluating GTV-to-CTV margin reduction in future clinical trials with the aim of limiting the cognitive sequelae of GBM irradiation while maintaining survival benefits of standard chemoradiation.

Clinical adoption patterns of 0.35 Tesla MR-guided radiation therapy in Europe and Asia.

BACKGROUND: Magnetic resonance-guided radiotherapy (MRgRT) utilization is rapidly expanding, driven by advanced capabilities including better soft tissue imaging, continuous intrafraction target visualization, automatic triggered beam delivery, and the availability of on-table adaptive replanning. Our objective was to describe patterns of 0.35 Tesla (T)-MRgRT utilization in Europe and Asia among early adopters of this novel technology. METHODS: Anonymized administrative data from all 0.35T-MRgRT treatment systems in Europe and Asia were extracted for patients who completed treatment from 2015 to 2020. Detailed treatment information was analyzed for all MR-linear accelerators (linac) and -cobalt systems. RESULTS: From 2015 through the end of 2020, there were 5796 completed treatment courses delivered in 46,389 individual fractions. 23.5% of fractions were adapted. Ultra-hypofractionated (UHfx) dose schedules (1-5 fractions) were delivered for 63.5% of courses, with 57.8% of UHfx fractions adapted on-table. The most commonly treated tumor types were prostate (23.5%), liver (14.5%), lung (12.3%), pancreas (11.2%), and breast (8.0%), with increasing compound annual growth rates (CAGRs) in numbers of courses from 2015 through 2020 (pancreas: 157.1%; prostate: 120.9%; lung: 136.0%; liver: 134.2%). CONCLUSIONS: This is the first comprehensive study reporting patterns of utilization among early adopters of a 0.35T-MRgRT system in Europe and Asia. Intrafraction MR image-guidance, advanced motion management, and increasing adoption of on-table adaptive RT have accelerated a transition to UHfx regimens. MRgRT has been predominantly used to treat tumors in the upper abdomen, pelvis and lungs, and increasingly with adaptive replanning, which is a radical departure from legacy radiotherapy practices.

Single-isocenter multiple-target stereotactic radiosurgery for multiple brain metastases: dosimetric evaluation of two automated treatment planning systems.

PURPOSE: Automated treatment planning systems are available for linear accelerator (linac)-based single-isocenter multi-target (SIMT) stereotactic radiosurgery (SRS) of brain metastases. In this study, we compared plan quality between Brainlab Elements Multiple Brain Metastases (Elements MBM) software which utilizes dynamic conformal arc therapy (DCAT) and Varian HyperArc (HA) software using a volumetric modulated arc therapy (VMAT) technique. PATIENTS AND METHODS: Between July 2018 and April 2021, 36 consecutive patients ≥ 18 years old with 367 metastases who received SIMT SRS at UPMC Hillman Cancer San Pietro Hospital, Rome, were retrospectively evaluated. SRS plans were created using the commercial software Elements MBM SRS (Version 1.5 and 2.0). Median cumulative gross tumor volume (GTV) and planning tumor volume (PTV) were 1.33 cm3 and 3.42 cm3, respectively. All patients were replanned using HA automated software. Extracted dosimetric parameters included mean dose (Dmean) to the healthy brain, volumes of the healthy brain receiving more than 5, 8,10, and 12 Gy (V5Gy, V8Gy, V10Gy and V12Gy), and doses to hippocampi. RESULTS: Both techniques resulted in high-quality treatment plans, although Element MBM DCAT plans performed significantly better than HA VMAT plans, especially in cases of more than 10 lesions). Median V12Gy was 13.6 (range, 1.87-45.9) cm3 for DCAT plans and 18.5 (2.2-62,3) cm3 for VMAT plans (p < 0.0001), respectively. Similarly, V10Gy, V8Gy, V5Gy (p < 0.0001) and median dose to the normal brain (p = 0.0001) were favorable for DCAT plans. CONCLUSIONS: Both Elements MBM and HA systems were able to generate high-quality plans in patients with up to 25 brain metastases. DCAT plans performed better in terms of normal brain sparing, especially in patients with more than ten lesions and limited total tumor volume.

Stereotactic or conventional radiotherapy for macroscopic prostate bed recurrence: a propensity score analysis.

PURPOSE: To assess outcomes between salvage radiation therapy (SRT) with curative intent and stereotactic radiotherapy for macroscopic prostate recurrence (SSRT) after radical prostatectomy (RP). In order to compare these two different options, we compared their outcomes with a propensity score-based matched analysis. METHODS: Data from 185 patients in seven Italian centres treated for macroscopic prostate bed recurrence after RP were retrospectively collected. To make a comparison between the two treatment groups, propensity matching was applied to create comparable cohorts. RESULTS: After matching, 90 patients in the SRT and SSRT groups were selected (45 in each arm). Kaplan-Meier analysis did not show any significant differences in terms of BRFS and PFS between matched populations (p = 0.08 and p = 0.8, respectively). Multivariate models show that treatment was not associated with BRFS, neither in the whole or matched cohort, with HR of 2.15 (95%CI 0.63-7.25, p = 0.21) and 2.65 (95%CI 0.59-11.97, p = 0.21), respectively. In the matched cohort, lower rate of toxicity was confirmed for patients undergoing SSRT, with acute GI and GU adverse events reported in 4.4 versus 44.4% (p < 0.001) and 28.9 versus 46.7% (p = 0.08) of patients, and late GI and GU adverse events reported in 0 versus 13.3% (p = 0.04) and 6.7 versus 22.2% (p = 0.03) of patients, respectively. CONCLUSION: Considering the favourable therapeutic ratio of this approach and the lower number of fractions needed, SSRT should be considered as an attractive alternative to conventional SRT in this setting.

Leptomeningeal disease and brain control after postoperative stereotactic radiosurgery with or without immunotherapy for resected brain metastases.

PURPOSE: Immunotherapy has shown activity in patients with brain metastases (BM) and leptomeningeal disease (LMD). We have evaluated LMD and intraparenchymal control rates for patients with resected BM receiving postoperative stereotactic radiosurgery (SRS) and immunotherapy or postoperative SRS alone. We hypothesize that postoperative SRS and immunotherapy will result in a lower rate of LMD with acceptable toxicity compared with postoperative SRS. PATIENTS AND METHODS: One hundred and twenty-nine patients with non-small-cell lung cancer (NSCLC) and melanoma BM who received postoperative fractionated SRS (fSRS; 3×9 Gy) in combination with immunotherapy or postoperative fSRS alone for completely resected BM were retrospectively evaluated. The primary endpoint of the study was the rate of LMD after treatments. The secondary endpoints were local failure, distant brain parenchymal failure (DBF), overall survival (OS), and treatment-related toxicity. RESULTS: Sixty-three patients received postoperative SRS and immunotherapy, either nivolumab or pembrolizumab, and 66 patients received postoperative SRS alone to the resection cavity. With a median follow-up of 15 months, LMD occurred in 19 patients: fSRS group, 14; fSRS and immunotherapy, 5. The 12-month LMD cumulative rates were 22% (95% CI 14% to 37%) in the fSRS group and 6% (95% CI 2% to 17%) in the combined treatment group (p=0.007). Resection cavity control was similar between the groups, whereas DBF and OS were significantly different; the 1-year DBF rates were 31% (95% CI 20% to 46%) in the fSRS and immunotherapy group and 52% (95% CI 39% to 68%) in the fSRS group; respective OS rates were 78% (95% CI 67% to 88%) and 58.7% (95% CI 47% to 70%). Twenty-two patients undergoing postoperative fSRS and immunotherapy and nine subjected to postoperative fSRS experienced treatment-related imaging changes suggestive of radiation-induced brain necrosis (p=0.02). CONCLUSIONS: Postoperative fSRS in combination with immunotherapy decreases the incidence of LMD and DBF in patients with resected BM from NSCLC and melanoma as compared with fSRS alone, reducing the rate of neurological death and prolonging survival.

Integrated care pathways and the hub-and-spoke model for the management of non-melanoma skin cancer: A proposal of the Italian Association of Hospital Dermatologists (ADOI).

The term non-melanoma skin cancer (NMSC) refers to skin cancer different from melanoma, and it is usually restricted to basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and their pre-cancerous lesions, e.g., actinic keratosis. These conditions represent the most frequent tumors in Caucasians and are characterized by an increasing incidence worldwide and a high socio-economic impact. The term Integrated Care Pathway (ICP) refers to "a complex intervention for the mutual decision making and organization of care processes for a well-defined group of patients during a well-defined period". The purpose of this paper is to present a proposal from the Italian Association of Hospital Dermatologists (ADOI) for an ICP organization of care of NMSC, considering the hub-and-spoke model in the different geographical areas. This proposal is based on the most recent literature and on documents from the Italian Association of Medical Oncology (AIOM), the European consensus-based interdisciplinary guidelines from the European Association of Dermato- Oncology (EADO), and the National Comprehensive Cancer Network (NCCN). We initially discuss the NMSC outpatient clinic, the role of the multidisciplinary working groups, and the hub-and-spoke model regarding this topic. Then, we define the ICP processes specific for BCC and SCC. The ICP for NMSC is an innovative strategy to guarantee the highest possible quality of health care while the hub-andspoke model is crucial for the organization of different health care structures. Considering the importance on this topic, it is essential to create a valid ICP together with an efficient organization within the different geographical areas.

Resilience in Radiotherapy Services During the COVID-19 Emergency: Collaboration Between the Regional Radiation Oncology Departments of Lazio, Abruzzo and Molise.

AIM: Radiation therapy is a cornerstone of oncological treatment and oncological patients show greater risk of developing complications related to COVID-19 infection. Stringent social restrictions have ensured a significant reduction in the spread of the virus, but also gave rise to a number of critical issues for radiation oncology wards. For this reason, the Directors of the Radiation Oncology Departments (RODs) of Lazio, Abruzzo and Molise regions shared their experience and ideas in order to create a common document that may assist in facing the negative impacts of the pandemic on radiation oncology wards and patients. PATIENTS AND METHODS: The study was conducted according to the Estimate-Talk-Estimate method. Five issues were proposed and rated. Among approved issues, statements were proposed anonymously, then harmonized and finally voted on according to a Likert scale from 1 to 9. Those for which an agreement of 7-9 was observed were finally approved. RESULTS: The document was developed with 42 statements dealing about safety measures for patients and staff, organization of clinical and work activities, usage of Information Technology systems for meetings/smart working. An agreement was recorded for 34 statements. CONCLUSION: This document sets out some recommendations for RODs and can provide valuable management information for Oncological Radiotherapy wards.

OLIGO-AIRO: a national survey on the role of radiation oncologist in the management of OLIGO-metastatic patients on the behalf of AIRO.

In the last years, several evidences demonstrated the role of stereotactic body radiotherapy (SBRT) in the oligometastatic disease and the possibility to increase survival in selected patients. In 2020 the study group "biology and treatment of the oligometastatic disease" of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) conducted a survey evaluating the attitude of physicians in treating the oligometastatic disease and the definition of it. An electronic questionnaire was administered online to the society members. 105 questionnaires were returned. 78% responders considered as oligometastatic a disease with ≤ 5 metastases. The majority of the responders (77%) treated > 50 patients in the last year, and 89% responders agreed in considering every oligometastatic tumor susceptible to local treatments. Regarding the clinical management of the oligometastatic disease, the majority of the responders (66%) suggested an interdisciplinary discussion. When choosing a treatment option for fit patients with a single oligometastatic focus, 52% of the responders agreed in proposing only SBRT. In the case of unfit patients with a single oligometastatic lesion the agreement was in favor of the SBRT alone (89%). In the oligoprogressive setting, 41% responders opted to continue the current systemic treatment and to add SBRT, while in the case of oligoresidual disease, 70% responders was in favor of adding SBRT and continuing the current systemic treatment. In conclusions, the survey illustrated the current agreement and prescribing attitude for oligometastatic patients in Italy. The non-homogenous agreement in some clinical scenarios suggest the need of more robust evidence.

Initial Experience With Single-Isocenter Radiosurgery to Target Multiple Brain Metastases Using an Automated Treatment Planning Software: Clinical Outcomes and Optimal Target Volume Margins Strategy.

PURPOSE: Our purpose was to assess the clinical outcomes and target positioning accuracy of frameless linear accelerator single-isocenter multiple-target (SIMT) dynamic conformal arc (DCA) stereotactic radiosurgery (SRS) for multiple brain metastases (BM). METHODS AND MATERIALS: Between October 2016 and September 2018, 31 consecutive patients ≥18 years old with 204 BM <3 cm in maximum size receiving SIMT DCA SRS were retrospectively evaluated. All plans were created using a dedicated automated treatment planning software (Brainlab, Munich, Germany), and treatments were performed with a Truebeam STx or a Novalis Tx (Brainlab and Varian Medical Systems, CA). The accuracy of setup and interfraction patient repositioning was assessed by Brainlab ExacTrac radiograph 6-dimensional image system and the risk of compromised target dose coverage evaluated. Brain control and overall survival were estimated by Kaplan-Meier method calculated from the time of SRS. RESULTS: Fourteen patients were treated for 4 to 6 and 17 patients for 7 to 10 BM. The mean gross tumor volume (GTV) was 0.65 cm3 and the mean planning target volume (PTV) was 0.89 cm3. Mean V95 (the volume of the PTV covered by 95% of the prescription dose) and D95 (the prescription dose covering 95% of the PTV) were 99.5% and 21.1 Gy, respectively. With a median clinical follow-up of 11 months (range, 4-26 months), the 1-year survival was 68% and local control was 89%. As a consequence of plan isocenter residual errors, a loss of target coverage, defined as V95 < 95%, occurred in 28 PTVs (10 patients); using a 1 mm GTV-to-PTV margin, adequate dose coverage was maintained for all lesions. CONCLUSIONS: SIMT DCA SRS represents a fast and effective approach for patients with up to 10 BM. The dosimetric effects of residual set-up and intrafraction positioning errors are modest, although a GTV-to-PTV margin of 1 mm is recommended.

A new standardized data collection system for brain stereotactic external radiotherapy: the PRE.M.I.S.E project.

BACKGROUND: In recent years, novel radiation therapy techniques have moved clinical practice toward tailored medicine. An essential role is played by the decision support system, which requires a standardization of data collection. The Aim of the Prediction Models In Stereotactic External radiotherapy (PRE.M.I.S.E.) project is the implementation of systems that analyze heterogeneous datasets. This article presents the project design, focusing on brain stereotactic radiotherapy (SRT). MATERIALS & METHODS: First, raw ontology was defined by exploiting semiformal languages (block and entity relationship diagrams) and the natural language; then, it was transposed in a Case Report Form, creating a storage system. RESULTS: More than 130 brain SRT's variables were selected. The dedicated software Beyond Ontology Awareness (BOA-Web) was set and data collection is ongoing. CONCLUSION: The PRE.M.I.S.E. project provides standardized data collection for a specific radiation therapy technique, such as SRT. Future aims are: including other centers and validating an extracranial SRT ontology.

Neurological outcome and memory performance in patients with 10 or more brain metastases treated with frameless linear accelerator (LINAC)-based stereotactic radiosurgery.

PURPOSE: To assess the neurocognitive function and neurological toxicity of frameless linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) in patients with 10 or more brain metastases (BM). PATIENTS AND METHODS: Forty consecutive adult patients who received SRS for ten or more 10 BM < 3 cm in maximum size were evaluated. All plans were generated using a single-isocenter multiple-target (SIMT) SRS technique with doses of 22 Gy for lesions < 2 cm and 16-18 Gy for those ≥ 2 cm in size. Survival analyses were estimated by Kaplan-Meier method from the date of SRS. Neurocognitive function using the Hopkins verbal learning test-revised (HVLT-R) and activity of daily living scale (ADLS) were collected prospectively at baseline and at 3,6 and 12-month follow-up. Toxicity was assessed by the National Cancer Institute Common Toxicity Criteria for Adverse Events (Version 5.0). RESULTS: With a median follow-up of 10.8 months, 1-year survival and local control rates were 65% and 86%, respectively. Grade 2 or 3 toxicity occurred in eleven patients, being associated with radiological changes suggestive of radiation necrosis in seven patients. Three months after SRS, the mean relative decline was 14.2% for HVLT-R delayed recall, 12.3% for HVLT-R recognition, and 9.8% for HVLT-R total recall. A significant deterioration of HVLT-R scores ranged from 5.5 to 18.7% of patients at different time points. ADLS scores declined over time, but changes were not significant. CONCLUSIONS: SRS is an effective and safe approach for patients with 10 or more BM able to maintain the pretreatment neurocognitive function in the majority of patients.

Stereotactic radiotherapy for prostate bed recurrence after prostatectomy, a multicentric series.

OBJECTIVE: To assess the safety and effectiveness of stereotactic salvage radiotherapy (SSRT) in RT-naïve patients affected by macroscopic prostate bed recurrence. PATIENTS AND METHODS: Consecutive patients treated for prostate bed macroscopic recurrence in three different Italian institutes were reviewed. Patients were treated with SSRT, with a total dose of 30-40 Gy in five fractions, the mean pre-SSRT PSA level was 2.3 ng/mL. Two different PSA thresholds were defined and biochemical recurrence-free survival (BCRFS) was reported, in order to better express outcome: BCRFS1 (a PSA level increase of >10% compared to the pre-SSRT value) and BCRFS2 (a PSA level increase of >0.2 ng/mL for patients with a PSA nadir of <0.2 ng/mL or two consecutive PSA level increases of >25% compared to nadir in patients with a PSA nadir of <0.2 ng/mL). RESULTS: In all, 90 patients were treated, with a mean (range) follow-up of 21.2 (2-64) months, and 17 of these patients (19%) had concomitant androgen-deprivation therapy (ADT) during SSRT. Complete biochemical response, defined as a PSA nadir of <0.2 ng/mL, was obtained in 39 of the 90 patients (43.3%). Considering BCRFS1, 25 patients (27.8%) had BCR, with an actuarial median BCRFS1 time of 36.4 months. For BCRFS2, BCR was reported in 32 patients (35.5%), with an actuarial median BCRFS2 time of 24.3 months. There was no Grade >2 toxicity. CONCLUSIONS: SSRT was found to yield significant biochemical control and allowed ADT delay despite adverse features.

Can thoracic nodes oligometastases be safely treated with image guided hypofractionated radiation therapy?

OBJECTIVE: To evaluate safety and efficacy of image guided-hypofractionated radiation therapy (IG-HRT) in patients with thoracic nodes oligometastases. METHODS: The present study is a multicenter analysis. Oligometastatic patients, affected by a maximum of five active lesions in three or less different organs, treated with IG-HRT to thoracic nodes metastases between 2012 and 2017 were included in the analysis. Primary end point was local control (LC), secondary end points were overall survival (OS), progression-free survival, acute and late toxicity. Univariate and multivariate analysis were performed to identify possible prognostic factors for the survival end points. RESULTS: 76 patients were included in the analysis. Different RT dose and fractionation schedules were prescribed according to site, number, size of the lymph node(s) and to respect dose constraints for relevant organs at risk. Median biologically effective dose delivered was 75 Gy (interquartile range: 59-86 Gy). Treatment was optimal; one G1 acute toxicity and seven G1 late toxicities of any grade were recorded. Median follow-up time was 23.16 months. 16 patients (21.05%) had a local progression, while 52 patients progressed in distant sites (68.42 %).Median local relapse free survival was not reached, LC at 6, 12 and 24 months was 96.05% [confidence interval (CI) 88.26-98.71%], 86.68% (CI 75.86-92.87) and 68.21% (CI 51.89-80.00%), respectively. Median OS was 28.3 months (interquartile range 16.1-47.2). Median progression-freesurvival was 9.2 months (interquartile range 4.1-17.93).At multivariate analysis, RT dose, colorectal histology, systemic therapies were correlated with LC. Performance status and the presence of metastatic sites other than the thoracic nodes were correlated with OS. Local response was a predictor of OS. CONCLUSION: IG-HRT for thoracic nodes was safe and feasible. Higher RT doses were correlated to better LC and should be taken in consideration at least in patients with isolated nodal metastases and colorectal histology. ADVANCES IN KNOWLEDGE: Radiotherapy is safe and effective treatment for thoracic nodes metastases, higher radiotherapy doses are correlated to better LC. Oligometastatic patients can receive IG-HRT also for thoracic nodes metastases.

Comparative effectiveness of multi-fraction stereotactic radiosurgery for surgically resected or intact large brain metastases from non-small-cell lung cancer (NSCLC).

PURPOSE: to investigate clinical outcomes in patients with large brain metastases from non-small-cell lung cancer (NSCLC) who received surgical resection and postoperative stereotactic radiosurgery or SRS alone. PATIENTS AND METHODS: Two hundred and twenty-two patients with 241 large brain metastases (2-4 cm in size) who received surgery and multi-fraction SRS (mfSRS) to the resection cavity or mfSRS alone were analyzed. For all lesions the delivered dose was 3 x 9 Gy over three consecutive days. Primary endpoint of the study was local control (LC). Secondary endpoints included early improvement of neurological deficits, changes in performance status, treatment-related toxicity, radiation-induced brain necrosis (RN), distant brain failure (DBF), and overall survival (OS). Kaplan-Meier analysis and cumulative incidence function were used for comparing the probability of failure. RESULTS: At a median follow-up of 13 months, median OS times and 1-year survival rates were comparable: 13.5 months and 59% for patients receiving surgery and postoperative mfSRS to the resection cavity and 15.2 months and 68% for those treated with mfSRS alone (p = 0.2). Median DBF did not differ significantly between groups (surgery and mfSRS,12 months; mfSRS,14 months). Eighteen patients receiving surgery and mfSRS and 17 patients treated with mfSRS alone recurred locally (p = 0.2); respective 6-month and 12-month LC rates were 87% and 83% and 96% and 91% (p = 0.15). The 1-year cumulative incidence rates of RN were 15% and 7% after postoperative mfSRS and mfSRS alone (p = 0.03), respectively. CONCLUSIONS: In conclusion, mfSRS is an effective treatment for patients with large brain metastases from NSCLC resulting in equivalent LC and lower RN and risk of leptomeningeal spread compared to surgery and mf-SRS to the resection cavity. Surgery is an effective treatment option for patients with large symptomatic brain metastases who require rapid relief of neurological symptoms caused by tumor mass effect.

Stereotactic ablative radiation therapy as a potential curative treatment in duodenal adenocarcinoma: a case report.

PURPOSE: One of the rarest gastrointestinal neoplasm is small bowel cancer. Experience with its treatment modalities is limited. Stereotactic ablative radiation therapy (SABR) has improved, with image-guided radiation therapy becoming a curative option in many tumors. Especially when surgery cannot be performed due to comorbidities, SABR provides a good toxicity profile and an excellent tumor control rate owing to its specific schedule: high dose on a limited and well-defined area. METHODS: An 83-year-old man had arterial hypertension and congestive cardiomyopathy, with recent history of upper abdominal pain, weight loss over 10 kg, and progressive severe fatigue. The patient underwent endoscopy that showed a large mass partially obstructing the second part of the duodenum; a biopsy revealed a moderately differentiated adenocarcinoma. A staging CT scan confirmed localized disease. Due to the patient's age and comorbidities, a SABR was proposed as the preferred treatment. In order to localize the tumor during radiotherapy sessions, surgical clips were placed endoscopically next to the lesion as fiducial markers. The patient received 25 Gy in 5 fractions on alternate days. RESULTS: Resolution of duodenal obstruction and bleeding lasted for 14 months. The patient died of myocardial infarction. CONCLUSIONS: This case suggests that SABR could have a role in the palliative treatment of small bowel cancers, with good toxicity profile, particularly in patients for whom surgical treatment is not a viable option.

High-dose radiotherapy plus prolonged hormone therapy in CT2-3 prostatic carcinoma: is it useful?

AIMS AND BACKGROUND: Clinical studies published in the last decade have shown the possible improvement in prognosis of patients with prostatic carcinoma undergoing radiation therapy with dose escalation or in combination with hormone therapy. However, in studies on hormone therapy, moderate doses of radiation therapy have been used, whereas in studies with high-dose radiotherapy, hormone therapy usually was not administered. Therefore, it is not clear whether the concomitant use of high doses and prolonged hormone therapy could determine an additional beneficial effect. The aim of the present study was therefore to evaluate the relative prognostic role of different dose levels (< 70 versus > or = 70 Gy) of external beam radiotherapy and of different hormone therapies (neoadjuvant only versus neoadjuvant + adjuvant). METHODS: A total of 426 patients (median age, 71 yrs; range, 51-87 yrs) underwent external beam radiotherapy (70 Gy median dose to prostate volume +/- 45 Gy to pelvic lymph nodes) and neoadjuvant hormone therapy (bicalutamide for 30 days; goserelin, 3.6 mg every 28 days starting two months before radiotherapy and for its entire duration). Dose to the prostate was < 70 Gy in 44.8% of patients and > or = 70 Gy in 55.2%. A total of 244 patients received adjuvant hormonal therapy. The distribution according to the clinical stage was 48.1% T2 and 51.9% T3. The distribution according to the Gleason score was 14.3% grades 2-4, 66.7% grades 5-7 and 19.0% grades 8-10. The distribution according to pretreatment prostate-specific antigen levels (in ng/mL) was 7.0% for 0-4, 29.3% for 4-10, 30.3% for 10-20, and 33.3% for > 20. RESULTS: With a median follow-up of 35 months (range, 1-151), 81 patients (19.0%) showed biochemical recurrence, 17 patients (4.0%) showed local disease progression, and 12 patients (2.8%) showed distant metastases. Overall, 23 patients (5.4%) showed disease progression. Four patients (0.9%) died. At the time of this writing, no patient has died from prostatic carcinoma. At univariate analysis, the radiation dose delivered to the tumor and the administration of adjuvant hormone therapy were shown to be significantly correlated with biochemical disease-free survival. At multivariate analysis, the single parameter significantly correlated with biochemical disease-free survival was the radiation dose delivered to the tumor. In the subset of patients not treated with adjuvant hormone therapy, there was a significant correlation between radiation dose and biochemical disease-free survival at univariate and multivariate analysis. A similar correlation between adjuvant hormone therapy and biochemical disease-free survival was observed in the subset of stage cT3 patients at univariate and multivariate analysis. In patients undergoing combined treatment without adjuvant hormone therapy, a significant correlation was observed between clinical stage and biochemical disease-free survival, at univariate and at multivariate analysis. CONCLUSIONS: The results of the study confirmed the positive impact of radiotherapy doses > 70 Gy and of adjuvant hormone therapy in patients with locally advanced prostatic carcinoma. Owing to the lack of evidence of a correlation between radiation dose and biochemical outcome in patients undergoing prolonged hormone therapy, the role of further dose escalation in patients undergoing combined hormone and radiation therapy is still unclear.