[Concurrent simultaneous integrated boost radiotherapy and cetuximab in head and neck squamous cell cancer patients: is it feasible in daily clinical practice?] / Radioterapia a intensità modulata con boost simultaneo più cetuximab in pazienti con carcinoma a cellule squamose in stadio localmente avanzato del distretto testa collo: è fattibile nella pratica clinica quotidiana?

INTRODUCTION AND AIM: Locally advanced head and neck squamous cell carcinoma (LA-Hnscc) is a true therapeutical challenge in the modern era and the scientific community is trying to face this challenge with new therapeutical strategies, including combinations of monoclonal antibodies and radiation therapy. The aim of this study is to evaluate clinical outcomes in LA-Hnscc patients unfit to receive platinum-based chemotherapy, treated with concurrent simultaneous integrated boost-intensity modulated radiotherapy (Sib-Imrt) + cetuximab (Ctx) in daily clinical practice. METHODS: LA-Hnscc patients not included in other prospective studies treated in 4 Italian radiotherapy units (2 Messina, 1 Rome, and 1 Lecce) using Sib-Imrt and Ctx were included in this study. Acute and late toxicities and overall survival (OS) have been evaluated. RESULTS: Data regarding 27 patients with squamous tumour were collected and reviewed. The primary tumour sites were oropharynx in 14 patients (51.9%), oral cavity in 7 (25.9%), larynx in 3 (11%) and other sites in 3(11%). There were 20 (74%) patients had stage IV (16 IVa and 4 IVb). Complete remission was observed in 18 patients (66.7%), a partial remission in 4 (14.8%) whilst 4 had a progression disease (14.8%). After 3 year of follow-up 7/27 patients were deaths. The OS was 95.5%, 62.5% and 52.9% respectively at 1,2 and 3 years. Acute toxicities were observed in all treated patients (mucositis, dermatitis and dysphagia) while 66.7% of patients developed late toxicities. All observed toxicities were grade 1 to 3 and just 1 patient developed a G4 toxicity. CONCLUSION: The concurrent bio-radiotherapy of Sib-Imrt and cetuximab is feasible in real-life daily clinical practice for LA-Hnscc patients unfit for platinum-based chemoradiotherapy.

A pharmacoeconomic analysis from Italian guidelines for the management of prolactinomas.

Background: Prolactinoma, the most common pituitary adenoma, is usually treated with dopamine agonist (DA) therapy like cabergoline. Surgery is second-line therapy, and radiotherapy is used if surgical treatment fails or in relapsing macroprolactinoma. Objective: This study aimed to provide economic evidence for the management of prolactinoma in Italy, using a cost-of-illness and cost-utility analysis that considered various treatment options, including cabergoline, bromocriptine, temozolomide, radiation therapy, and surgical strategies. Methods: The researchers conducted a systematic literature review for each research question on scientific databases and surveyed a panel of experts for each therapeutic procedure's specific drivers that contributed to its total cost. Results: The average cost of the first year of treatment was €2,558.91 and €3,287.40 for subjects with microprolactinoma and macroprolactinoma, respectively. Follow-up costs from the second to the fifth year after initial treatment were €798.13 and €1,084.59 per year in both groups. Cabergoline had an adequate cost-utility profile, with an incremental cost-effectiveness ratio (ICER) of €3,201.15 compared to bromocriptine, based on a willingness-to-pay of €40,000 per quality-adjusted life year (QALY) in the reference economy. Endoscopic surgery was more cost-effective than cabergoline, with an ICER of €44,846.64. Considering a willingness-to-pay of €40,000/QALY, the baseline findings show cabergoline to have high cost utility and endoscopic surgery just a tad above that. Conclusions: Due to the favorable cost-utility profile and safety of surgical treatment, pituitary surgery should be considered more frequently as the initial therapeutic approach. This management choice could lead to better outcomes and an appropriate allocation of healthcare resources.

Italian Guidelines for the Management of Prolactinomas.

INTRODUCTION: This guideline (GL) is aimed at providing a reference for the management of prolactin (PRL)-secreting pituitary adenoma in adults. However, pregnancy is not considered. METHODS: This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinologi (AME) has identified potentially relevant outcomes, which have then been rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" have been considered in the systematic review of evidence and only those classified as "critical" have been considered in the formulation of recommendations. RESULTS: The present GL provides recommendations regarding the role of pharmacological and neurosurgical treatment in the management of prolactinomas. We recommend cabergoline (Cab) vs. bromocriptine (Br) as the firstchoice pharmacological treatment to be employed at the minimal effective dose capable of achieving the regression of the clinical picture. We suggest that medication and surgery are offered as suitable alternative first-line treatments to patients with non-invasive PRL-secreting adenoma, regardless of size. We suggest Br as an alternative drug in patients who are intolerant to Cab and are not candidates for surgery. We recommend pituitary tumor resection in patients 1) without any significant neuro-ophthalmologic improvement within two weeks from the start of Cab, 2) who are resistant or do not tolerate Cab or other dopamine-agonist drugs (DA), 3) who escape from previous efficacy of DA, and 4) who are unwilling to undergo a chronic DA treatment. We recommend that patients with progressive disease notwithstanding previous tumor resection and ongoing DA should be managed by a multidisciplinary team with specific expertise in pituitary diseases using a multimodal approach that includes repeated surgery, radiotherapy, DA, and possibly, the use of temozolomide. CONCLUSION: The present GL is directed to endocrinologists, neurosurgeons, and gynecologists working in hospitals, in territorial services or private practice, and to general practitioners and patients.

Image-guided robotic radiosurgery for the treatment of arteriovenous malformations.

BACKGROUND: Cerebral arteriovenous malformations (AVMs) are challenging lesions, often requiring multimodal interventions; however, data on the efficacy of stereotactic radiosurgery for cerebral AVMs are limited. This study aimed to evaluate the clinical and radiographic results following robotic radiosurgery, alone or in combination with endovascular treatment, and to investigate factors associated with obliteration and complications in patients with AVM. METHODS: We retrospectively analyzed the clinical and imaging characteristics of 123 patients with AVMs of all Spetzler-Martin grades treated at two institutions by robotic radiosurgery in single-fraction doses (CyberKnife). Embolization was performed before radiosurgery in a subset of patients to attempt to downgrade the lesions. Factors associated with AVM obliteration and complications (toxicity) were identified via univariate and multivariate analyses. RESULTS: The median follow-up time was 48.1 months (range, 3.6-123 months). Five patients were lost to follow-up. The obliteration rate in the 59 patients with a follow-up period exceeding four years was 72.8%. Complete obliteration and partial remission were achieved in 67 (56.8%) and 31 (26.3%) cases, respectively, whereas no change was observed in 20 cases (17.8%). Embolization was performed in 54/123 cases (43.9%). Complete and partial obliteration were achieved in 29 (55.7%) and 14 (26.9%) embolized patients, respectively. In the multivariate analysis, the factors associated with obliteration were age (p = .018) and the Spetzler-Martin grade (p = .041). Treatment-induced toxicity (radiation necrosis and/or edema) was observed in 15 cases (12.7%), rebleeding occurred in three cases (2.5%), and the rate of mortality associated with rebleeding was 1.7%. CONCLUSIONS: CyberKnife radiosurgery is a valid approach for treating AVMs of all Spetzler-Martin-grades, with satisfactory obliteration rates, low toxicity, and a relatively rare incidence of rebleeding.

Spine eburnation in a metastatic lung cancer patient treated with immunotherapy and radiotherapy. The first case report of bystander effect on bone.

INTRODUCTION: Metastatic non-small cell lung cancer (NSCLC) is nowadays treated with a multimodal therapeutic approach including immunotherapy, targeted therapy and radiotherapy. Radiation therapy, in addition to immune checkpoint inhibitors, gives rise to a particular radiobiological effect known as "bystander effect" consisting of the radiation-induced damage in nearby unirradiated cells. CASE REPORT: We report a case of a 79-year-old female patient with stage IV NSCLC treated with concomitant immuno-radiotherapy who showed a bystander effect on bone.Management and outcome: Primary tumour biopsy revealed an adenocarcinoma with a PDL1 expression >50%, while staging exams showed a right pulmonary lesion with a partial involvement of the contiguous rib and a single brain metastasis. The patient refused chemotherapy, so that Pembrolizumab 2 mg/Kg was administered every 3 weeks. After two administrations, the single brain metastasis was treated using stereotactic radiosurgery while the site of primitive lung cancer received an 8 Gy-single fraction 3 D-conformal radiotherapy. Three months after irradiation a chest CT showed a radiological remission of about 10% of the GTV and a partial eburnation of the vertebra located nearby the target volume. The CT images of a PET/CT at six months showed a complete vertebral eburnation. At the last follow-up, the patient was free of disease (brain MRI, spinal MRI and PET/CT). DISCUSSION: The present case alerts for unusual side effects provoked by bystander phenomenon in patients treated with a combination of immunotherapy and irradiation. Immune activation exacerbates the bystander effect causing normal tissues toxicities beyond what immunotherapies are causing by themselves.

Curative Radiotherapy in Elderly Patients With Muscle Invasive Bladder Cancer: The Prognostic Role of Sarcopenia.

BACKGROUND/AIM: To evaluate the impact of sarcopenia in muscle invasive bladder cancer (MIBC) elderly patients submitted to curative radiotherapy. PATIENTS AND METHODS: Patients received radiotherapy between 2013 and 2018, and the skeletal muscle index was calculated to classify them as sarcopenic or non-sarcopenic. Primary endpoints were overall survival (OS), cancer specific survival (CSS), 90-day mortality and toxicity. RESULTS: A total of 28 patients with a median age of 85 years met our inclusion criteria and 8 of them were sarcopenic. With a median prescribed dose of 61 Gy and a median follow-up of 24.5 months, OS rates in the sarcopenic and non-sarcopenic groups were 100% and 84.4% at 3 months, 57.1% and 56.6% at 12 months, 38.1% and 50.3% at 24 months and 38.1% and 33.5% at 48 months, respectively; the CSS rates were 100% and 94.1% at 3 months and 68.6% and 88.2% at 12, 24 and 48 months, respectively. The actuarial 90-day mortality rate was 17.9% for the whole cohort, and 20% and 12.5% for the non-sarcopenic and sarcopenic groups, respectively. The radio-induced toxicity was similar in both groups. CONCLUSION: Sarcopenia cannot be considered a negative prognostic factor for MIBC elderly patients treated with external beam radiotherapy. Irradiation is therefore a feasible and effective choice for these patients, especially if unfit for surgery.

Image-Guided Multisession Radiosurgery of Skull Base Meningiomas.

BACKGROUND: The efficacy of single-session stereotactic radiosurgery (sSRS) for the treatment of intracranial meningioma is widely recognized. However, sSRS is not always feasible in cases of large tumors and those lying close to critically radiation-sensitive structures. When surgery is not recommended, multi-session stereotactic radiosurgery (mSRS) can be applied. Even so, the efficacy and best treatment schedule of mSRS are not yet established. The aim of this study is to validate the role of mSRS in the treatment of skull base meningiomas. METHODS: A retrospective analysis of patients with skull base meningiomas treated with mSRS (two to five fractions) at the University of Messina, Italy, from 2008 to 2018, was conducted. RESULTS: 156 patients met the inclusion criteria. The median follow-up period was 36.2 ± 29.3 months. Progression-free survival at 2-, 5-, and 10- years was 95%, 90%, and 80.8%, respectively. There were no new visual or motor deficits, nor cranial nerves impairments, excluding trigeminal neuralgia, which was reported by 5.7% of patients. One patient reported carotid occlusion and one developed brain edema. CONCLUSION: Multisession radiosurgery is an effective approach for skull base meningiomas. The long-term control is comparable to that obtained with conventionally-fractionated radiotherapy, while the toxicity rate is very limited.

Factors affecting outcome in frameless non-isocentric stereotactic radiosurgery for trigeminal neuralgia: a multicentric cohort study.

BACKGROUND: Stereotactic radiosurgery (SRS) is an effective treatment for trigeminal neuralgia (TN). Nevertheless, a proportion of patients will experience recurrence and treatment-related sensory disturbances. In order to evaluate the predictors of efficacy and safety of image-guided non-isocentric radiosurgery, we analyzed the impact of trigeminal nerve volume and the nerve dose/volume relationship, together with relevant clinical characteristics. METHODS: Two-hundred and ninety-six procedures were performed on 262 patients at three centers. In 17 patients the TN was secondary to multiple sclerosis (MS). Trigeminal pain and sensory disturbances were classified according to the Barrow Neurological Institute (BNI) scale. Pain-free-intervals were investigated using Kaplan Meier analyses. Univariate and multivariate Cox regression analyses were performed to identify predictors. RESULTS: The median follow-up period was 38 months, median maximal dose 72.4 Gy, median target nerve volume 25 mm3, and median prescription dose 60 Gy. Pain control rate (BNI I-III) at 6, 12, 24, 36, 48, and 60 months were 96.8, 90.9, 84.2, 81.4, 74.2, and 71.2%, respectively. Overall, 18% of patients developed sensory disturbances. Patients with volume ≥ 30 mm3 were more likely to maintain pain relief (p = 0.031), and low integral dose (< 1.4 mJ) tended to be associated with more pain recurrence than intermediate (1.4-2.7 mJ) or high integral dose (> 2.7 mJ; low vs. intermediate: log-rank test, χ2 = 5.02, p = 0.019; low vs. high: log-rank test, χ2 = 6.026, p = 0.014). MS, integral dose, and mean dose were the factors associated with pain recurrence, while re-irradiation and MS were predictors for sensory disturbance in the multivariate analysis. CONCLUSIONS: The dose to nerve volume ratio is predictive of pain recurrence in TN, and re-irradiation has a major impact on the development of sensory disturbances after non-isocentric SRS. Interestingly, the integral dose may differ significantly in treatments using apparently similar dose and volume constraints.

COVID-19 outbreak and cancer radiotherapy disruption in Italy: Survey endorsed by the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

Italy experienced one of the world's deadliest COVID-19 outbreaks and healthcare systems had to instantly reorganise activity. The Italian Radiation Oncology Departments adapted numerous solutions to minimize the disruptions. Information technologies, treatment prioritization and implementation of hypofractionation and protection procedures allowed balancing between cancer patient care and patient/healthcare workers safety.

Simultaneous Integrated Boost Radiotherapy in Unresectable Stage IV (M0) Head and Neck Squamous Cell Cancer Patients: Daily Clinical Practice.

AIM: To evaluate clinical outcome in locally-advanced stage IV (M0) head and neck cancer patients treated using intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) in daily clinical practice. BACKGROUND: Despite SIB-IMRT has been reported as a feasible and effective advanced head and neck cancer treatment, there are few data about its concurrent use with systemic therapies. MATERIAL AND METHODS: We reviewed 41 staged IV (M0) head and neck cancer patients treated in two radiotherapy units in the city of Messina (Italy) during the last six years, using intensity modulated techniques-SIB. 22/41 patients had concomitant chemotherapy or cetuximab. Acute and late toxicities, objective response (OR) rate, local control (LC) and overall survival (OS) have been evaluated. RESULTS: 37/41 patients received the planned doses of radiotherapy, 2 patients died during the therapy. The major acute regional toxicities were skin reaction and mucositis. A case of mandibular osteoradionecrosis was recorded. At completion of treatment, OR was evaluated in 38 patients: 32/38 patients (84.2%) had complete (55.3%) and partial (28.9%) response. The 1- and 5-year LC rates were 73.4% and 69.73%, respectively. The 1-, 3-, and 5-year OS rates were 85.93%, 51.49% and 44.14%, respectively. No statistically significant differences in outcomes have been observed in patients treated with radiotherapy alone vs. irradiation concomitant to chemo/biotherapy. The median OS was 45 months. CONCLUSION: SIB-IMRT is safeand can be used with concomitant chemotherapy/biotherapy in real-life daily clinical practice. SIB-IMRT alone is a valid alternative in patients unfit for systemic therapies.

Stereotactic Body Radiation Therapy With Simultaneous Integrated Boost in Patients With Spinal Metastases.

Stereotactic body radiation therapy in patients with spine metastases maximizes local tumor control and preserves neurologic function. A novel approach could be the use of stereotactic body radiation therapy with simultaneous integrated boost delivering modality. The aim of the present study is to report our experience in the treatment of spine metastases using a frameless radiosurgery system delivering stereotactic body radiation therapy-simultaneous integrated boost technique. The primary endpoints were the pain control and the time to local progression; the secondary ones were the overall survival and toxicity. A total of 20 patients with spine metastases and 22 metastatic sites were treated in our center with stereotactic body radiation therapy-simultaneous integrated boost between December 2007 and July 2018. Stereotactic body radiation therapy-simultaneous integrated boost treatments were delivered doses of 8 to 10 Gy in 1 fraction to isodose line of 50%. The median follow-up was 35 months (range: 12-110). The median time to local progression for all patients was not reached and the actuarial 1-, 2-, and 3-years local free progression rate was 86.36%. In 17 of 20 patients, a complete pain remission was observed and 3 of 20 patients had a partial pain remission (complete pain remission + partial pain remission: 100%). The median overall survival was 38 months (range 12-83). None of the patients experienced neither radiation adverse events (grade 1-4) nor reported pain flair reaction. None of the patients included in our series experienced vertebral compression fracture. Spine radiosurgery with stereotactic body radiation therapy-simultaneous integrated boost is safe. The use of this modality in spine metastases patients provides an excellent local control.

Stereotactic body radiation therapy and radiofrequency ablation for the treatment of liver metastases: How and when?

Limited liver metastases represent a clinical challenge. Surgical approach is the most frequently reported treatment option, however, some patients are not eligible for surgical interventions. Relatively recent technologic advances have permitted the safe use of ablative techniques employed in the cure of hepatic metastases. Among these, radiofrequency ablation (RFA) and stereotactic body radiotherapy (SBRT) have emerged as valid treatments in a significant proportion of patients with intrahepatic oligometastatic disease. This review offers an up-to-date of current available literature on this issue focusing on the use and outcomes of RFA and SBRT, according to the PICO (Population, Intervention, Comparison and Outcomes) criteria.

DCE and DSC perfusion MRI diagnostic accuracy in the follow-up of primary and metastatic intra-axial brain tumors treated by radiosurgery with cyberknife.

BACKGROUND: The differential diagnosis between radiation necrosis, tumor recurrence and tumor progression is crucial for the evaluation of treatment response and treatment planning. The appearance of treatment-induced tissue necrosis on conventional Magnetic Resonance Imaging (MRI) is similar to brain tumor recurrence and it could be difficult to differentiate the two entities on follow-up MRI examinations. Dynamic Susceptibility Contrast-enhanced (DSC) and Dynamic Contrast-Enhanced (DCE) are MRI perfusion techniques that use an exogenous, intravascular, non-diffusible gadolinium-based contrast agent. The aim of this study was to compare the diagnostic accuracy of DSC and DCE perfusion MRI in the differential diagnosis between radiation necrosis and tumor recurrence, in the follow-up of primary and metastatic intra-axial brain tumors after Stereotactic RadioSurgery (SRS) performed with CyberKnife. METHODS: A total of 72 enhancing lesions (57 brain metastases and 15 primary brain tumors) were analyzed with DCE and DSC, by means of MRI acquisition performed by 1,5 Tesla MR scanner. The statistical relationship between the diagnosis of tumor recurrence or radiation necrosis, decided according to clinicoradiologically criteria, rCBV and Ktrans was evaluated by the point-biserial correlation coefficient respectively. RESULTS: The statistical analysis showed a correlation between the diagnosis of radiation necrosis or recurrent tumor with Ktrans (rpb = 0.54, p < 0.001) and with rCBV (rpb = 0.37, p = 0.002). The ROC analysis of rCBV values demonstrated a good classification ability in differentiating radiation necrosis from tumour recurrence as well as the Ktrans. The optimal cut-off value for rCBV was k = 1.23 with 0.88 of sensitivity and 0.75 of specificity while for Ktrans was k = 28.76 with 0.89 of sensitivity and 0.97 of specificity. CONCLUSIONS: MRI perfusion techniques, particularly DCE, help in the differential diagnosis by tumor recurrence and radiation necrosis during the follow-up after radiosurgery.

Clinical Evaluation of Low-Molecular-Weight Hyaluronic Acid-Based Treatment on Onset of Acute Side Effects in Women Receiving Adjuvant Radiotherapy after Cervical Surgery: A Randomized Clinical Trial.

BACKGROUND: Radiotherapy treatment for cervical cancer (CC) often induces side effects, including inflammation, dryness, dyspareunia. Considering its key role in the healing process, hyaluronic acid (HA) could be useful for the completion of radiotherapy. OBJECTIVES: The aim of this work was to evaluate the ability of HA to reduce the onset of side effects due to radiotherapy. MATERIALS AND METHODS: In total, 180 women undergoing radiotherapy were randomized into two arms: controls and those treated with vaginal suppositories containing low-molecular-weight HA from day 1 of radiotherapy. The study lasted 5 weeks and was characterized by three visits: at baseline (T0), 15 days later (T1), and at the end of the radiotherapy cycle (T2). The onset of side effects, pain, safety, efficacy, acceptability of treatment, and compliance to the therapy were evaluated. RESULTS: Patients in the control arm reported the onset and worsening of all symptoms with a moderate or severe grade at T2, whereas in the treatment arm almost 90% of patients reported the absence of symptoms or a mild grade. All patients in the treatment arm referred a lower intensity of pain on a visual analog scale compared with the control arm at T2 (6.85 ± 0.94 vs. 1.88 ± 1.02). CONCLUSIONS: HA was able to help vaginal mucosa healing during radiotherapy in patients with CC.

Frameless Stereotactic Radiosurgery for Treatment of Multiple Sclerosis-Related Trigeminal Neuralgia.

BACKGROUND: Trigeminal neuralgia (TN) affects 7% of patients with multiple sclerosis (MS). In such patients, TN is difficult to manage either pharmacologically and surgically. Radiosurgical rhizotomy is an effective treatment option. The nonisocentric geometry of radiation beams of CyberKnife introduces new concepts in the treatment of TN. Its efficacy for MS-related TN has not yet been demonstrated. METHODS: Twenty-seven patients with refractory TN and MS were treated. A nonisocentric beams distribution was chosen; the maximal target dose was 72.5 Gy. The maximal dose to the brainstem was <12 Gy. Effects on pain, medications, sensory disturbance, rate, and time of pain recurrence were analyzed. RESULTS: Median follow-up was 37 (18-72) months. Barrow Neurological Institute pain scale score I-III was achieved in 23/27 patients (85%) within 45 days. Prescription isodose line (80%) accounting for a dose of 58 Gy incorporated an average of 4.85 mm (4-6 mm) of the nerve and mean nerve volume of 26.4 mm3 (range 20-38 mm3). Seven out of 27 patients (26%) had mild, not bothersome, facial numbness (Barrow Neurological Institute numbness score II). The rate of pain control decreased progressively after the first year, and only 44% of patients retained pain control 4 years later. CONCLUSIONS: Frameless radiosurgery can be effectively used to perform retrogasserian rhizotomy. Pain relief was satisfactory and, with our dose/volume constraints, no sensory complications were recorded. Nonetheless, long-term pain control was possible in less than half of the patients. This is a limitation that CyberKnife radiosurgery shares with other techniques in MS patients.

3D-Printing of Arteriovenous Malformations for Radiosurgical Treatment: Pushing Anatomy Understanding to Real Boundaries.

Radiosurgery of arteriovenous malformations (AVMs) is a challenging procedure. Accuracy of target volume contouring is one major issue to achieve AVM obliteration while avoiding disastrous complications due to suboptimal treatment. We describe a technique to improve the understanding of the complex AVM angioarchitecture by 3D prototyping of individual lesions. Arteriovenous malformations of ten patients were prototyped by 3D printing using 3D rotational angiography (3DRA) as a template. A target volume was obtained using the 3DRA; a second volume was obtained, without awareness of the first volume, using 3DRA and the 3D-printed model. The two volumes were superimposed and the conjoint and disjoint volumes were measured. We also calculated the time needed to perform contouring and assessed the confidence of the surgeons in the definition of the target volumes using a six-point scale. The time required for the contouring of the target lesion was shorter when the surgeons used the 3D-printed model of the AVM (p=0.001). The average volume contoured without the 3D model was 5.6 ± 3 mL whereas it was 5.2 ± 2.9 mL with the 3D-printed model (p=0.003). The 3D prototypes proved to be spatially reliable. Surgeons were absolutely confident or very confident in all cases that the volume contoured using the 3D-printed model was plausible and corresponded to the real boundaries of the lesion. The total cost for each case was 50 euros whereas the cost of the 3D printer was 1600 euros. 3D prototyping of AVMs is a simple, affordable, and spatially reliable procedure that can be beneficial for radiosurgery treatment planning. According to our preliminary data, individual prototyping of the brain circulation provides an intuitive comprehension of the 3D anatomy of the lesion that can be rapidly and reliably translated into the target volume.