Structural insights into the binding of bS1 to the ribosome.

The multidomain ribosomal protein bS1 is the biggest and the most flexible and dynamic protein in the 30S small subunit. Despite being essential for mRNA recruitment and its primary role in the accommodation of the start codon within the decoding centre, there has not yet been a high-resolution description of its structure. Here, we present a 3D atomic model of OB1 and OB2, bS1's first two N-terminal domains, bound to an elongation-competent 70S ribosome. Our structure reveals that, as previously reported, bS1 is anchored both by a π-stacking to the 30S subunit and via a salt bridge with the Zn2+ pocket of bS1. These contacts are further stabilized by other interactions with additional residues on OB1. Our model also shows a new conformation of OB2, interacting with the Shine-Dalgarno portion of the mRNA. This study confirms that OB1 plays an anchoring role, but also highlights a novel function for OB2, which is directly involved in the modulation and support of mRNA binding and accommodation on the ribosome.

Insights into the ribosomal trans-translation rescue system: lessons from recent structural studies.

The arrest of protein synthesis caused when ribosomes stall on an mRNA lacking a stop codon is a deadly risk for all cells. In bacteria, this situation is remedied by the trans-translation quality control system. Trans-translation occurs because of the synergistic action of two main partners, transfer-messenger RNA (tmRNA) and small protein B (SmpB). These act in complex to monitor protein synthesis, intervening when necessary to rescue stalled ribosomes. During this process, incomplete nascent peptides are tagged for destruction, problematic mRNAs are degraded and the previously stalled ribosomes are recycled. In this 'Structural Snapshot' article, we describe the mechanism at the molecular level, a view updated after the most recent structural studies using cryo-electron microscopy.

A Combined Hypofractionated Volumetric Modulated Arc Radiotherapy, Radio-Sensitising and Adjuvant Metronomic Chemotherapy Treatment for Canine Stage IV Nasal Tumours With Intracranial Extension.

Radiation therapy has become the standard of care in the treatment of canine intranasal neoplasia, but because of the poor prognosis associated with stage IV nasal tumours and the proximity of the brain to the irradiation target, few data regarding the treatment of very advanced neoplasms are available. The aim of this pilot study was to evaluate the feasibility, safety and effectiveness of a combined treatment composed of definitive high-dose hypofractionated volumetric modulated arc radiotherapy on tumours with concurrent treatment of regional lymph nodes if positive or as prophylaxis, carboplatin radio-sensitising, and adjuvant metronomic chemotherapy for stage IV canine nasal tumours with intracranial extension. A pilot observational study was conducted in 7 dogs. Magnetic resonance imaging follow-up examinations revealed complete responses in 5 dogs and partial responses in 2. The median overall survival time, evaluated via Kaplan-Meier survival analysis, was 310 days with a 95% confidence interval of 210-400 days, whereas the median progression-free survival was 240 days with a 95% confidence interval of 190-290 days. Despite the proximity of highly sensitive organs at risk, no grade III or IV toxicities were observed, and volumetric modulated arc radiotherapy seemed to be a feasible treatment option for stage IV canine nasal tumours where conformal 3D radiotherapy has proven to give higher doses with severe damage to the surrounding unaffected tissues. Further studies are needed on the role of the sphenoid bone microscopic infiltration and regional lymph node involvement. The absence of severe toxicity could also lead to a dose escalation study and chemotherapy scheme.

Cranial Spinal Spreading of Canine Brain Gliomas after Hypofractionated Volumetric-Modulated Arc Radiotherapy and Concomitant Temozolomide Chemotherapy: A Four-Case Report.

Gliomas are the second-most-common primary brain tumors in dogs. Surgery and radiotherapy are established treatment approaches with similar median survival time, whereas conventional chemotherapy is burdened by severe adverse effects. Spinal and leptomeningeal spread of gliomas have been described following radiotherapy treatment alone. The purpose of this study was to evaluate the outcome for four dogs with primary high-grade gliomas in the forebrain without evidence, at diagnosis, of neoplastic invasion along the spinal cord, that were treated with concomitant chemotherapy (temozolomide) and hypofractionated volumetric-modulated arc radiotherapy (VMAT-RT). Temozolomide was selected for its radiosensitive properties, and radiotherapy dose protocols of 37 Gy in 7 fractions or 42 Gy in 10 fractions were used. After an initial complete or partial response, tumors recurred across the cranial-spinal pathway. Post-mortem macroscopic examinations confirmed swollen spinal cord and hyperemic meningeal sleeve, with nodular lesions on the meningeal surface. Microscopically, infiltration of the spinal cord and meninges by neoplastic cells (with features of oligodendrogliomas) were observed. This work seems to suggest that the entire central nervous system should be investigated in diagnostic examinations of canine gliomas. Dose-escalation trials and/or spinal cord prophylaxis treatment could also be evaluated to prevent tumor progression.

Substrate recognition and cryo-EM structure of the ribosome-bound TAC toxin of Mycobacterium tuberculosis.

Toxins of toxin-antitoxin systems use diverse mechanisms to control bacterial growth. Here, we focus on the deleterious toxin of the atypical tripartite toxin-antitoxin-chaperone (TAC) system of Mycobacterium tuberculosis, whose inhibition requires the concerted action of the antitoxin and its dedicated SecB-like chaperone. We show that the TAC toxin is a bona fide ribonuclease and identify exact cleavage sites in mRNA targets on a transcriptome-wide scale in vivo. mRNA cleavage by the toxin occurs after the second nucleotide of the ribosomal A-site codon during translation, with a strong preference for CCA codons in vivo. Finally, we report the cryo-EM structure of the ribosome-bound TAC toxin in the presence of native M. tuberculosis cspA mRNA, revealing the specific mechanism by which the TAC toxin interacts with the ribosome and the tRNA in the P-site to cleave its mRNA target.

Analysis of the Structure-Function-Dynamics Relationships of GALT Enzyme and of Its Pathogenic Mutant p.Q188R: A Molecular Dynamics Simulation Study in Different Experimental Conditions.

The third step of the catabolism of galactose in mammals is catalyzed by the enzyme galactose-1-phosphate uridylyltransferase (GALT), a homodimeric enzyme with two active sites located in the proximity of the intersubunit interface. Mutations of this enzyme are associated to the rare inborn error of metabolism known as classic galactosemia; in particular, the most common mutation, associated with the most severe phenotype, is the one that replaces Gln188 in the active site of the enzyme with Arg (p.Gln188Arg). In the past, and more recently, the structural effects of this mutation were deduced on the static structure of the wild-type human enzyme; however, we feel that a dynamic view of the proteins is necessary to deeply understand their behavior and obtain tips for possible therapeutic interventions. Thus, we performed molecular dynamics simulations of both wild-type and p.Gln188Arg GALT proteins in the absence or in the presence of the substrates in different conditions of temperature. Our results suggest the importance of the intersubunit interactions for a correct activity of this enzyme and can be used as a starting point for the search of drugs able to rescue the activity of this enzyme in galactosemic patients.

Simulation of the Interactions of Arginine with Wild-Type GALT Enzyme and the Classic Galactosemia-Related Mutant p.Q188R by a Computational Approach.

Classic galactosemia is an inborn error of metabolism associated with mutations that impair the activity and the stability of galactose-1-phosphate uridylyltransferase (GALT), catalyzing the third step in galactose metabolism. To date, no treatments (including dietary galactose deprivation) are able to prevent or alleviate the long-term complications affecting galactosemic patients. Evidence that arginine is able to improve the activity of the human enzyme expressed in a prokaryotic model of classic galactosemia has induced researchers to suppose that this amino acid could act as a pharmacochaperone, but no effects were detected in four galactosemic patients treated with this amino acid. Given that no molecular characterizations of the possible effects of arginine on GALT have been performed, and given that the samples of patients treated with arginine are extremely limited for drawing definitive conclusions at the clinical level, we performed computational simulations in order to predict the interactions (if any) between this amino acid and the enzyme. Our results do not support the possibility that arginine could function as a pharmacochaperone for GALT, but information obtained by this study could be useful for identifying, in the future, possible pharmacochaperones for this enzyme.

Structures of tmRNA and SmpB as they transit through the ribosome.

In bacteria, trans-translation is the main rescue system, freeing ribosomes stalled on defective messenger RNAs. This mechanism is driven by small protein B (SmpB) and transfer-messenger RNA (tmRNA), a hybrid RNA known to have both a tRNA-like and an mRNA-like domain. Here we present four cryo-EM structures of the ribosome during trans-translation at resolutions from 3.0 to 3.4 Å. These include the high-resolution structure of the whole pre-accommodated state, as well as structures of the accommodated state, the translocated state, and a translocation intermediate. Together, they shed light on the movements of the tmRNA-SmpB complex in the ribosome, from its delivery by the elongation factor EF-Tu to its passage through the ribosomal A and P sites after the opening of the B1 bridges. Additionally, we describe the interactions between the tmRNA-SmpB complex and the ribosome. These explain why the process does not interfere with canonical translation.

A combined protocol with piroxicam, chemotherapy, and whole pelvic irradiation with simultaneous boost volumetric modulated arc radiotherapy for muscle-invasive canine urinary transitional cell carcinoma: First clinical experience.

The aims of this pilot study were to evaluate the feasibility and efficacy of high-dose hypofractionated volumetric modulated arc radiotherapy (VMAT) applied to whole pelvic region radiotherapy (WPRT) with multilevel simultaneous integrated boost (MLSIB) combined with piroxicam and chemotherapy for the treatment of canine transitional cell carcinoma (TCC) of the lower urinary tract with muscle invasion TCC. Twelve dogs were enrolled, according to stage, in two groups: group 1, TCC confined to the urinary tract; group 2, TCC with metastasis. The planning target volume dose was tailored from 36 to 42 Gy in 6 fractions. All dogs were prescribed piroxicam and radiosensitizing carboplatin, and six received chemotherapy after radiotherapy. Serial follow-ups with computed tomography and magnetic resonance imaging were performed. Disease control and toxicity effects were evaluated according to the Response Evaluation Criteria in Solid Tumors and Veterinary Radiation Therapy Oncology Group criteria. The treatment was well tolerated, and no high-grade side effects were reported. The median overall survival times for groups 1 and 2 were 1,230 and 150 days, respectively. A considerable percentage of patients in group1 (50%) were still alive at the time of writing this paper, and a longer follow-up could enable a more accurate survival analysis. This preliminary analysis shows that VMAT applied to the WPRT with MLSIB is an effective and safe option for dogs with lower urinary TCC, although the presence of metastases worsens the prognosis.

Trans-Translation Is an Appealing Target for the Development of New Antimicrobial Compounds.

Because of the ever-increasing multidrug resistance in microorganisms, it is crucial that we find and develop new antibiotics, especially molecules with different targets and mechanisms of action than those of the antibiotics in use today. Translation is a fundamental process that uses a large portion of the cell's energy, and the ribosome is already the target of more than half of the antibiotics in clinical use. However, this process is highly regulated, and its quality control machinery is actively studied as a possible target for new inhibitors. In bacteria, ribosomal stalling is a frequent event that jeopardizes bacterial wellness, and the most severe form occurs when ribosomes stall at the 3'-end of mRNA molecules devoid of a stop codon. Trans-translation is the principal and most sophisticated quality control mechanism for solving this problem, which would otherwise result in inefficient or even toxic protein synthesis. It is based on the complex made by tmRNA and SmpB, and because trans-translation is absent in eukaryotes, but necessary for bacterial fitness or survival, it is an exciting and realistic target for new antibiotics. Here, we describe the current and future prospects for developing what we hope will be a novel generation of trans-translation inhibitors.

High dose hypofractionated frameless volumetric modulated arc radiotherapy is a feasible method for treating canine trigeminal nerve sheath tumors.

The aim of this prospective pilot study was to evaluate the feasibility and effectiveness of curative intent high dose hypofractionated frameless volumetric modulated arc radiotherapy for treatment of canine trigeminal peripheral nerve sheath tumors. Client-owned dogs with a presumptive imaging-based diagnosis of trigeminal peripheral nerve sheath tumor were recruited for the study during the period of February 2010 to December 2013. Seven dogs were enrolled and treated with high dose hypofractionated volumetric modulated arc radiotherapy delivered by a 6 MV linear accelerator equipped with a micro-multileaf beam collimator. The plans were computed using a Monte Carlo algorithm with a prescription dose of 37 Gy delivered in five fractions on alternate days. Overall survival was estimated using a Kaplan-Meier curve analysis. Magnetic resonance imaging (MRI) follow-up examinations revealed complete response in one dog, partial response in four dogs, and stable disease in two dogs. Median overall survival was 952 days with a 95% confidence interval of 543-1361 days. Volumetric modulated arc radiotherapy was demonstrated to be feasible and effective for trigeminal peripheral nerve sheath tumor treatment in this sample of dogs. The technique required few sedations and spared organs at risk. Even though larger studies are required, these preliminary results supported the use of high dose hypofractionated volumetric modulated arc radiotherapy as an alternative to other treatment modalities.

Stereotactic Volume Modulated Arc Radiotherapy in Canine Meningiomas: Imaging-Based and Clinical Neurological Posttreatment Evaluation.

A prospective study to assess high-dose hypofractionated volume modulated arc radiotherapy feasibility and efficacy in canine meningiomas was conducted. Thirty-nine patients with encephalic and spinal meningiomas assumed from MRI findings were recruited and received high-dose hypofractionated volumetric modulated arc radiotherapy by a linear accelerator equipped with an external beam modulator micro-multileaf collimator and an XVI cone beam computed tomography system. The prescribed mean dose was 33 Gy in five fractions. The treatment feasibility was tested through planned and delivered dose agreement checks. Regular clinical examinations were performed during and after irradiation time, with regard to mentation, deambulation, cranial nerve dysfunction, and seizures. Serial MRI exams were done 60 days after irradiation and after 4, 6, 12, 18, and 24 mo. Volumetric disease reduction criteria implemented with clinical neurological systematic evaluation were adopted to assess the course and to categorize patients' responses. Complete and partial responses were observed on the whole in 65.5% of alive patients 24 mo after irradiation. Two-yr overall and disease-specific survival rates were 74.3% and 97.4%, respectively, and the putative radiotoxic effects were found to be few and slight.

Volumetric Modulated Arc (Radio) Therapy in Pets Treatment: The "La Cittadina Fondazione" Experience.

Volumetric Modulated Arc Therapy (VMAT) is a modern technique, widely used in human radiotherapy, which allows a high dose to be delivered to tumor volumes and low doses to the surrounding organs at risk (OAR). Veterinary clinics takes advantage of this feature due to the small target volumes and distances between the target and the OAR. Sparing the OAR permits dose escalation, and hypofractionation regimens reduce the number of treatment sessions with a simpler manageability in the veterinary field. Multimodal volumes definition is mandatory for the small volumes involved and a positioning device precisely reproducible with a setup confirmation is needed before each session for avoiding missing the target. Additionally, the elaborate treatment plan must pursue hard constraints and objectives, and its feasibility must be evaluated with a per patient quality control. The aim of this work is to report results with regard to brain meningiomas and gliomas, trigeminal nerve tumors, brachial plexus tumors, adrenal tumors with vascular invasion and rabbit thymomas, in comparison with literature to determine if VMAT is a safe and viable alternative to surgery or chemotherapy alone, or as an adjuvant therapy in pets.

Frameless stereotactic volumetric modulated arc radiotherapy of brachial plexus tumours in dogs: 10 cases.

OBJECTIVE: Treatment of canine peripheral nerve sheath tumours (PNSTs) is challenging and prognosis after surgical resection is considered poor. The aim of this study was to evaluate the feasibility and effectiveness of stereotactic radiotherapy (RT) of these tumours. METHODS: 10 dogs with clinical symptoms and MRI findings consistent with PNSTs of the brachial plexus, branches and nerve roots were treated with linear accelerator-based volumetric-modulated arc radiotherapy (VMAT) with a dose of 35 Gy/5 fractions. Clinical and MRI follow-up examinations were planned and radiotoxicity and survival times were investigated. RESULTS: Tumours involved the plexus and proximal nerves in three dogs, the plexus, proximal nerves and nerve roots in five dogs and the nerve roots and proximal nerves in two dogs. Partial response and partial or complete reductions of neurological deficits were observed in all the treated dogs. Local recurrence was observed in 9/10 of treated dogs. No symptom directly referable to radiotoxicity was observed. Mean overall survival of 371 ± 30 days [95% confidence interval (CI) of (315-427)] and mean progression-free survival of 240 ± 30 days (95% CI of 188-291) from this work are comparable with surgical literature data regarding the plexus and proximal nerve localization, but are superior in comparison with nerve root localization. CONCLUSION: VMAT can be a safe and viable alternative to surgery in cases of canine brachial plexus PNSTs involving the proximal nerves and nerve roots. Advances in knowledge: To our knowledge, this is the first prospective observational clinical study regarding VMAT stereotactic RT treatment for canine brachial plexus PNSTs and suggests that VMAT may achieve at least similar clinical outcome than surgery in a safer way.

FEASIBILITY FOR USING HYPOFRACTIONATED STEREOTACTIC VOLUMETRIC MODULATED ARC RADIOTHERAPY (VMAT) WITH ADAPTIVE PLANNING FOR TREATMENT OF THYMOMA IN RABBITS: 15 CASES.

Thymoma is a relatively common tumor in rabbits. Treatment with surgery, radiation therapy, and chemotherapy alone or in combination has been reported with varying outcomes. Stereotactic volumetric modulated arc radiotherapy delivered in a hypofractionated manner allows high doses of radiation to be delivered to the target volume while allowing sparing of adjacent critical structures. This therapy is ideally suited for thymomas in rabbits given their size, the difficulty of multiple anesthesia episodes and the complexity of the radiotherapy plans required due to the tumor's proximity to the heart, lungs, and mediastinal structures. Fifteen rabbits with thymoma were prospectively recruited for this observational, single institution, single arm clinical study. All rabbits were imaged with both computed tomography (CT) and magnetic resonance imaging (MRI). A total dose of 40 Gy in six fractions was delivered using a single arc over an 11-day period with repeat CT simulation done every other fraction for adaptive planning. Follow-up evaluation was done through repeat CT and MRI imaging and revealed complete responses using the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Two rabbits had died at 618 and 718 days, 10 were alive and three were lost to follow-up. Observed acute and late effects were graded according to the Veterinary Radiation Therapy Oncology Group (VRTOG) criteria and were found to be minimal.

Volumetric modulation arc radiotherapy compared with static gantry intensity-modulated radiotherapy for malignant pleural mesothelioma tumor: a feasibility study.

PURPOSE: A planning study was performed to evaluate RapidArc (RA), a volumetric modulated arc technique, on malignant pleural mesothelioma. The benchmark was conventional fixed-field intensity-modulated radiotherapy (IMRT). METHODS AND MATERIALS: The computed tomography data sets of 6 patients were included. The plans for IMRT with nine fixed beams were compared against double-modulated arcs with a single isocenter. All plans were optimized for 15-MV photon beams. The dose prescription was 54 Gy to the planning target volume. The planning objectives for the planning target volume were a minimal dose of >95% and maximal dose of <107%. For the organs at risk, the parameters were as follows: contralateral lung, percentage of volume receiving 5 Gy (V(5 Gy)) <60%, V(20 Gy) < 10%, mean <10.0 Gy; liver, V(30 Gy) <33%, mean <31 Gy; heart, V(45 Gy) <30%, V(50 Gy) <20%, dose received by 1% of the volume (D(1%)) <60 Gy; contralateral kidney, V(15 Gy) <20%; spine, D(1%) <45 Gy; esophagus, V(55 Gy) <30%; and spleen, V(40 Gy) <50%. The monitor units (MUs) and delivery time were scored to measure the treatment efficiency. The pretreatment portal dosimetry scored delivery to the calculation agreement with the Gamma Agreement Index. RESULTS: RA and IMRT provided equivalent coverage and homogeneity. Both techniques fulfilled objectives on organs at risk with a tendency of RA to improve sparing. The conformity index was 1.9 +/- 0.1 for RA and IMRT. The number of MU/2 Gy was 734 +/- 82 for RA and 2,195 +/- 317 for IMRT. The planning vs. delivery agreement revealed a Gamma Agreement Index for IMRT of 96.0% +/- 2.6% and for RA of 95.7% +/- 1.5%. The treatment time was 3.7 +/- 0.3 min for RA and 13.4 +/- 0.1 min for IMRT. CONCLUSION: RA demonstrated compared with conventional IMRT, similar target coverage and better dose sparing to the organs at risks. The number of MUs and the time required to deliver a 2-Gy fraction were much lower for RA, allowing the possibility to incorporate this technique in the treatment options for mesothelioma patients.

Applying failure mode effects and criticality analysis in radiotherapy: lessons learned and perspectives of enhancement.

INTRODUCTION: The radiation oncology process along with its unique therapeutic properties is also potentially dangerous for the patient, and thus it should be delivered under a systematic risk control. To this aim incident reporting and analysis are not sufficient for assuring patient safety and proactive risk assessment should also be implemented. The paper accounts for some methodological solutions, lessons learned and opportunities for improvement, starting from the systematic application of the failure mode effects and criticality analysis (FMECA) technique to the radiotherapy process of an Italian hospital. MATERIALS AND METHODS: The analysis, performed by a working group made of experts of the radiotherapy unit, was organised into the following steps: (1) complete and detailed analysis of the process (integration definition for function modelling); (2) identification of possible failure modes (FM) of the process, representing sources of adverse events for the patient; (3) qualitative risk assessment of FMs, aimed at identifying priorities of intervention; (4) identification and planning of corrective actions. RESULTS: Organisational and procedural corrective measures were implemented; a set of safety indexes for the process was integrated within the traditional quality assurance indicators measured by the unit. A strong commitment of all the professionals involved was observed and the study revealed to be a powerful "tool" for dissemination of patient safety culture. CONCLUSION: The feasibility of FMECA in fostering radiotherapy safety was proven; nevertheless, some lessons learned as well as weaknesses of current practices in risk management open to future research for the integration of retrospective methods (e.g. incident reporting or root cause analysis) and risk assessment.

Re-irradiation of metastatic spinal cord compression: a feasibility study by volumetric-modulated arc radiotherapy for in-field recurrence creating a dosimetric hole on the central canal.

When local recurrences arise within an irradiated region involving metastatic spinal cord compression, the dose limit to the spinal cord reduces the chance to re-treat the patient by 3D-conformational RT technique. The possibility of using volumetric modulated arc RT by RapidArc was evaluated for dose sparing at spinal cord level and preserving target coverage. A clinically satisfactory PTV coverage and dose sparing to the spinal cord were obtained. An upcoming trial on patients will provide clinical outcomes.

Critical appraisal of volumetric modulated arc therapy in stereotactic body radiation therapy for metastases to abdominal lymph nodes.

PURPOSE: A planning study was performed comparing volumetric modulated arcs, RapidArc (RA), fixed beam IMRT (IM), and conformal radiotherapy (CRT) with multiple static fields or short conformal arcs in a series of patients treated with hypofractionated stereotactic body radiation therapy (SBRT) for solitary or oligo-metastases from different tumors to abdominal lymph nodes. METHODS AND MATERIALS: Fourteen patients were included in the study. Dose prescription was set to 45 Gy (mean dose to clinical target volume [CTV]) in six fractions of 7.5 Gy. Objectives for CTV and planning target volume (PTV) were as follows: Dose(min) >95%, Dose(max) <107%. For organs at risk the following objectives were used: Maximum dose to spine <18 Gy; V(15Gy) <35% for both kidneys, V(36Gy) <1% for duodenum, V(36Gy) <3% for stomach and small bowel, V(15Gy) <(total liver volume--700 cm(3)) for liver. Dose-volume histograms were evaluated to assess plan quality. RESULTS: Planning objectives on CTV and PTV were achieved by all techniques. Use of RA improved PTV coverage (V(95%) = 90.2% +/- 5.2% for RA compared with 82.5% +/- 9.6% and 84.5% +/- 8.2% for CRT and IM, respectively). Most planning objectives for organs at risk were met by all techniques except for the duodenum, small bowel, and stomach, in which the CRT plans exceeded the dose/volume constraints in some patients. The MU/fraction values were as follows: 2186 +/- 211 for RA, 2583 +/- 699 for IM, and 1554 +/- 153 for CRT. Effective treatment time resulted as follows: 3.7 +/- 0.4 min for RA, 10.6 +/- 1.2 min for IM, and 6.3 +/- 0.5 min for CRT. CONCLUSIONS: Delivery of SBRT by RA showed improvements in conformal avoidance with respect to standard conformal irradiation. Delivery parameters confirmed logistical advantages of RA, particularly compared with IM.

Hypofractionated stereotactic radiotherapy and radiosurgery for the treatment of patients with radioresistant brain metastases.

AIM: To evaluate the efficacy of different radiotherapy treatment modalities in radioresistant brain metastasis. PATIENTS AND METHODS: A retrospective analysis was conducted on 78 patients with brain metastases from melanoma, sarcoma, or renal cell carcinoma primary tumours who underwent radiosurgery (20 Gy) and/or hypofractionated stereotactic radiotherapy (6x4 Gy or 7x4 Gy) with or without whole-brain radiotherapy at our Center. RESULTS: The actuarial median survival times for melanoma, renal cell carcinoma and sarcoma were 23, 22 and 7 months respectively, with a significant correlation to recursive partitioning analysis class. DISCUSSION: Our results show that these treatments were effective both in symptom palliation and in improving survival, suggesting that although outcomes generally remained poor in this study population, it is possible and important to control intracranial brain metastases.