Multisession radiosurgery for grade 2 (WHO), high risk meningiomas. A phase II clinical trial.

PURPOSE: Patients suffering from recurrent and residual grade 2 (WHO) meningiomas after subtotal excision should be considered as high-risk groups with an uncertain prognosis. Adjuvant radiotherapy seems to be the best approach to reduce disease progression. The primary aim of this phase II explorative, monocentric, single arm study was to evaluate the safety of adjuvant multisession radiosurgery (mRS) in this group of patients; the efficacy in terms of tumour local control was the secondary endpoint. METHODS: Patients recruited from April 2017 to May 2019 were over 18 years old, had a histologically-documented intracranial recurrent or residual Grade 2 meningioma (WHO 2016) and a KPS > 70. Patients with NF2, concomitant neoplasm or pregnancy were excluded. Descriptive statistics were provided for categorical variables. Progression free survival (PFS) was modelled using the Kaplan-Meier method. RESULTS: Twenty-four patients were enrolled. All 24 patients underwent mRS: twenty-two patients received 28 Gy in 4 fractions, 2 patients received 24 Gy in 4 Treatment related adverse events (CTCAE 4.3) were limited to grade 2 in 1 patient (4.1%). At a median follow-up of 28 months, 8 patients (33.3%) had disease progression, either out-of-field or infield, compared with the planning target volume. Considering both infield and out-of-field progressions, 3-year PFS was 47% (95% confidence interval, CI, 22-69%); considering only the infield ones, 3-year PFS was 86% (95% CI 55-96%), and local control at last follow-up was 92%. CONCLUSION: mRS provides good local control of the tumour volume (TV) and is associated with a low rate of toxicity. These results call for further investigation to confirm favourable outcomes in patients with high-risk meningioma. TRIAL INFORMATION: NCT05081908, October 18, 2021, retrospectively registered.

Radiosurgery for trigeminal neuralgia: the state of art.

The trigeminal neuralgia (TN) is a chronic, episodic, and disabling facial pain syndrome. It is a relatively rare disorder. Despite this, because of the intensity of the pain, TN may have a dramatic impact for many patients. Fortunately, most of the patients may obtain a good pain relief simply by taking drugs. Historically, the surgical approaches represent a true treatment paradigm for all the drug-resistant TN. In this context, radiosurgery (RS) is a relatively new treatment modality. The effectiveness and safety of radiosurgery are today widely accepted and the technique can be proposed to many patients which suffer from a drug-resistant TN. This is true especially when the patients are less than ideal candidates for an open surgery, or for elderly ones, when a clear neuro-vascular conflict is not evident. The present review provides a concise analysis of the actual indications for radiosurgery, as well as the most acknowledged prognostic factors. The pathogenesis of TN and the rationale for the RS efficacy are also investigated and described. Some technical aspects including the target selection and the prescription doses, which have widely changed in time, are depicted. In conclusion, the present review supports the idea that TN is a complex disease and radiosurgery represents an effective and relatively new treatment modality, which enriches the treatment armamentarium for these unfortunate patients. To optimize the RS results, a correct patient selection has to be performed.

Sum signal dosimetry: A new approach for high dose quality assurance with Gafchromic EBT3.

Gafchromic EBT3 film dosimetry in radiosurgery (RS) and hypofractionated radiotherapy (HRT) is complicated by the limited film accuracy at high fractional doses. The aim of this study is to develop and evaluate sum signal (SS) film dosimetry to increase dose resolution at high fractional doses, thus allowing for use of EBT3 for dose distribution verification of RS/HRT treatments. To characterize EBT3 dose-response, a calibration was performed in the dose range 0.44-26.43 Gy. Red (RC) and green (GC) channel net optical densities were linearly added to produce the SS. Dose resolution and overall accuracy of the dosimetric protocol were estimated and compared for SS,RC, and GC. A homemade Matlab software was developed to compare, in terms of gamma analysis, dose distributions delivered by a Cyberknife on EBT3 films to dose distributions calculated by the treatment planning system. The new SS and conventional single channel (SC) methods were compared, using 3%/1 and 4%/1 mm acceptance criteria, for 20 patient plans. Our analysis shows that the SS dose-response curve is characterized by a steeper trend in comparison with SC, with SS providing a higher dose resolution in the whole dose range investigated. Gamma analysis confirms that the percentage of points satisfying the agreement criteria is significantly higher for SS compared to SC: 95.03% vs. 88.41% (P = 0.014) for 3%/1 mm acceptance criteria and 97.24% vs. 93.58% (P = 0.048) for 4%/1 mm acceptance criteria. This study demonstrates that the SS approach is a new and effective method to improve dosimetric accuracy in the framework of the RS-HRT patient-specific quality assurance protocol.

Focused ultrasound therapy in movement disorders: management roadmap toward optimal pathway organization.

MRI-guided focused ultrasound (MRgFUS) lesioning is an innovative, safe and effective treatment which provides an innovative development in the field of minimally invasive stereotactic neurosurgery. Based on the application of focused ultrasound energy under full MR planning and thermal imaging control, unilateral lesioning of the thalamus, subthalamic nucleus, and globus pallidus is indicated for the treatment of movement disorders, including essential tremor, Parkinson's disease, and dystonia. We started to apply this technique in February 2019 for the treatment of patients with movement disorders. The authors developed a diagnostic therapeutic care pathway, which is herewith proposed and applied as an explication of standard clinical practice in use. The project was the result of the application of different methods such as Health Technology Assessment (HTA), Strengths, Weaknesses, Opportunities and Threats analysis (SWOT) and Demin -Plan, Do, Check, Act (PDCA) cycle. The aim of this project was to standardize the MRgFUS diagnostic-therapeutic pathway (DTP), describe its application and the appropriateness of different phases (patient selection, intervention phase and follow-up). Here, we described in detail our experience in the DTP application from 2019 up to now in 610 patients with movement disorders.

Intradural extramedullary benign spinal lesions radiosurgery. Medium- to long-term results from a single institution experience.

BACKGROUND: Surgery represents the first-choice treatment for spinal intradural tumours. On the other hand, whether it is most appropriate in the setting of recurrences, residual or multiple lesions remains an open question. Moreover, some patients are less than ideal candidates for surgery. In this study we report about our own radiosurgery experience in the treatment of benign intradural extramedullary tumours of the spine. METHODS: In our study we analyzed the outcomes for 18 patients (21 lesions) treated for benign intradural extramedullary lesions, with a minimum follow-up period of 32 months. The lesions included 11 meningiomas, 9 schwannomas and 1 neurofibroma. RESULTS: The mean follow-up was 43 months (32-73 months). The median tumour volume was 2 cc (0.2-17.7 cc). Eleven lesions underwent single-fraction treatment (mean prescribed dose ranging from 10 to 13 Gy). The others received a multisession radiosurgery treatment (4-6 fractions) with a mean prescription dose ranging from 18.5 to 25 Gy. The maximum dose to the spinal cord ranged from 9.2 to 26 Gy. During the follow-up period, none of the lesions showed radiological evidence of progression. Neurological status was preserved or improved and no permanent sequelae were observed. Significant and durable pain relief was observed. CONCLUSIONS: Although surgical excision remains the primary treatment option for most intradural tumours, radiosurgery offers a real alternative therapeutic modality, especially in case of recurrent and residual lesions or when surgery is contraindicated.

Development of Predictive Models for the Response of Vestibular Schwannoma Treated with Cyberknife®: A Feasibility Study Based on Radiomics and Machine Learning.

PURPOSE: to predict vestibular schwannoma (VS) response to radiosurgery by applying machine learning (ML) algorithms on radiomic features extracted from pre-treatment magnetic resonance (MR) images. METHODS: patients with VS treated with radiosurgery in two Centers from 2004 to 2016 were retrospectively evaluated. Brain T1-weighted contrast-enhanced MR images were acquired before and at 24 and 36 months after treatment. Clinical and treatment data were collected contextually. Treatment responses were assessed considering the VS volume variation based on pre- and post-radiosurgery MR images at both time points. Tumors were semi-automatically segmented and radiomic features were extracted. Four ML algorithms (Random Forest, Support Vector Machine, Neural Network, and extreme Gradient Boosting) were trained and tested for treatment response (i.e., increased or non-increased tumor volume) using nested cross-validation. For training, feature selection was performed using the Least Absolute Shrinkage and Selection Operator, and the selected features were used as input to separately build the four ML classification algorithms. To overcome class imbalance during training, Synthetic Minority Oversampling Technique was used. Finally, trained models were tested on the corresponding held out set of patients to evaluate balanced accuracy, sensitivity, and specificity. RESULTS: 108 patients treated with Cyberknife® were retrieved; an increased tumor volume was observed at 24 months in 12 patients, and at 36 months in another group of 12 patients. The Neural Network was the best predictive algorithm for response at 24 (balanced accuracy 73% ± 18%, specificity 85% ± 12%, sensitivity 60% ± 42%) and 36 months (balanced accuracy 65% ± 12%, specificity 83% ± 9%, sensitivity 47% ± 27%). CONCLUSIONS: radiomics may predict VS response to radiosurgery avoiding long-term follow-up as well as unnecessary treatment.

Fifty Shades of Erns: Innate Immune Evasion by the Viral Endonucleases of All Pestivirus Species.

The genus Pestivirus, family Flaviviridae, includes four historically accepted species, i.e., bovine viral diarrhea virus (BVDV)-1 and -2, classical swine fever virus (CSFV), and border disease virus (BDV). A large number of new pestivirus species were identified in recent years. A common feature of most members is the presence of two unique proteins, Npro and Erns, that pestiviruses evolved to regulate the host's innate immune response. In addition to its function as a structural envelope glycoprotein, Erns is also released in the extracellular space, where it is endocytosed by neighboring cells. As an endoribonuclease, Erns is able to cleave viral ss- and dsRNAs, thus preventing the stimulation of the host's interferon (IFN) response. Here, we characterize the basic features of soluble Erns of a large variety of classified and unassigned pestiviruses that have not yet been described. Its ability to form homodimers, its RNase activity, and the ability to inhibit dsRNA-induced IFN synthesis were investigated. Overall, we found large differences between the various Erns proteins that cannot be predicted solely based on their primary amino acid sequences, and that might be the consequence of different virus-host co-evolution histories. This provides valuable information to delineate the structure-function relationship of pestiviral endoribonucleases.

Positively Charged Amino Acids in the Pestiviral Erns Control Cell Entry, Endoribonuclease Activity and Innate Immune Evasion.

The genus Pestivirus, family Flaviviridae, includes four economically important viruses of livestock, i.e., bovine viral diarrhea virus-1 (BVDV-1) and -2 (BVDV-2), border disease virus (BDV) and classical swine fever virus (CSFV). Erns and Npro, both expressed uniquely by pestiviruses, counteract the host's innate immune defense by interfering with the induction of interferon (IFN) synthesis. The structural envelope protein Erns also exists in a soluble form and, by its endoribonuclease activity, degrades immunostimulatory RNA prior to their activation of pattern recognition receptors. Here, we show that at least three out of four positively-charged residues in the C-terminal glycosaminoglycan (GAG)-binding site of BVDV-Erns are required for efficient cell entry, and that a positively charged region more upstream is not involved in cell entry but rather in RNA-binding. Moreover, the C-terminal domain on its own determines intracellular targeting, as GFP fused to the C-terminal amino acids of Erns was found at the same compartments as wt Erns. In summary, RNase activity and uptake into cells are both required for Erns to act as an IFN antagonist, and the C-terminal amphipathic helix containing the GAG-binding site determines the efficiency of cell entry and its intracellular localization.

Benefit of Bovine Viral Diarrhoea (BVD) Eradication in Cattle on Pestivirus Seroprevalence in Sheep.

Bovine viral diarrhoea virus (BVDV) and Border disease virus (BDV) are closely related pestiviruses of cattle and sheep, respectively. Both viruses may be transmitted between either species, but control programs are restricted to BVDV in cattle. In 2008, a program to eradicate bovine viral diarrhoea (BVD) in cattle was started in Switzerland. As vaccination is prohibited, the cattle population is now widely naïve to pestivirus infections. In a recent study, we determined that nearly 10% of cattle are positive for antibodies to BDV. Here, we show that despite this regular transmission of BDV from small ruminants to cattle, we could only identify 25 cattle that were persistently infected with BDV during the last 12 years of the eradication program. In addition, by determining the BVDV and BDV seroprevalence in sheep in Central Switzerland before and after the start of the eradication, we provide evidence that BVDV is transmitted from cattle to sheep, and that the BVDV seroprevalence in sheep significantly decreased after its eradication in cattle. While BDV remains endemic in sheep, the population thus profited at least partially from BVD eradication in cattle. Importantly, on a national level, BVD eradication does not appear to be generally derailed by the presence of pestiviruses in sheep. However, with every single virus-positive cow, it is necessary to consider small ruminants as a potential source of infection, resulting in costly but essential investigations in the final stages of the eradication program.

On the evaluation of edgeless diode detectors for patient-specific QA in high-dose stereotactic radiosurgery.

PURPOSE: In this work, the potential of an innovative "edgeless" silicon diode was evaluated as a response to the still unmet need of a reliable tool for plan dosimetry verification of very high dose, non-coplanar, patient-specific radiosurgery treatments. In order to prove the effectiveness of the proposed technology, we focused on radiosurgical treatments for functional disease like tremor or pain. METHODS: The edgeless diodes response has been validated with respect to clinical practice standard detectors by reproducing the reference dosimetry data adopted for the Treatment Planning System. In order to evaluate the potential for radiosurgery patient-specific treatment plan verification, the anthropomorphic phantom Alderson RANDO has been adopted along with three edgeless sensors, one placed in the centre of the Planning Target Volume, one superiorly and one inferiorly. RESULTS: The reference dosimetry data obtained from the edgeless detectors are within 2.6% for output factor, off-axis ratio and well within 2% for tissue phantom ratio when compared to PTW 60,018 diode. The edgeless detectors measure a dose discrepancy of approximately 3.6% from the mean value calculated by the TPS. Larger discrepancies are obtained in very steep gradient dose regions when the sensors are placed outside the PTV. CONCLUSIONS: The angular independent edgeless diode is proposed as an innovative dosimeter for patient quality assurance of brain functional disorders and other radiosurgery treatments. The comparison of the diode measurements with TPS calculations confirms that edgeless diodes are suitable candidates for patient-specific dosimetric verification in very high dose ranges delivered by non-isocentric stereotactic radiosurgery modalities.

Additive Fabrication of a Vascular 3D Phantom for Stereotactic Radiosurgery of Arteriovenous Malformations.

In this study, an efficient methodology for manufacturing a realistic three-dimensional (3D) cerebrovascular phantom resembling a brain arteriovenous malformation (AVM) for applications in stereotactic radiosurgery is presented. The AVM vascular structure was 3D reconstructed from brain computed tomography (CT) data acquired from a patient. For the phantom fabrication, stereolithography was used to produce the AVM model and combined with silicone casting to mimic the brain parenchyma surrounding the vascular structure. This model was made with tissues-equivalent materials for radiology. The hollow vascular system of the phantom was filled with a contrast agent usually employed on patients for CT scans. The radiological response of the phantom was tested and compared with the one of the clinical case. The constructed model demonstrated to be a very accurate physical representation of the AVM and its vasculature and good morphological consistency was observed between the model and the patient-specific source anatomy. These results suggest that the proposed method has potential to be used to fabricate patient-specific phantoms for neurovascular radiosurgery applications and medical research.

Artificial intelligence applications in medical imaging: A review of the medical physics research in Italy.

PURPOSE: To perform a systematic review on the research on the application of artificial intelligence (AI) to imaging published in Italy and identify its fields of application, methods and results. MATERIALS AND METHODS: A Pubmed search was conducted using terms Artificial Intelligence, Machine Learning, Deep learning, imaging, and Italy as affiliation, excluding reviews and papers outside time interval 2015-2020. In a second phase, participants of the working group AI4MP on Artificial Intelligence of the Italian Association of Physics in Medicine (AIFM) searched for papers on AI in imaging. RESULTS: The Pubmed search produced 794 results. 168 studies were selected, of which 122 were from Pubmed search and 46 from the working group. The most used imaging modality was MRI (44%) followed by CT(12%) ad radiography/mammography (11%). The most common clinical indication were neurological diseases (29%) and diagnosis of cancer (25%). Classification was the most common task for AI (57%) followed by segmentation (16%). 65% of studies used machine learning and 35% used deep learning. We observed a rapid increase of research in Italy on artificial intelligence in the last 5 years, peaking at 155% from 2018 to 2019. CONCLUSIONS: We are witnessing an unprecedented interest in AI applied to imaging in Italy, in a diversity of fields and imaging techniques. Further initiatives are needed to build common frameworks and databases, collaborations among different types of institutions, and guidelines for research on AI.

Helical tomotherapy for scalp recurrence of primary eccrine mucinous adenocarcinoma.

Primary cutaneous mucinous carcinomas originating from sweat glands are rare tumors with patterns of spread that are difficult to predict. We present a case of a five times recurring eccrine mucinous adenocarcinoma of the scalp, previously treated with surgery and adjuvant radiation therapy. After magnetic resonance imaging (MRI) and 18F-fluoro-2-deoxyglucose positron-emission tomography/computed tomography (18FDG-PET/CT), which documented local recurrence, the patient was considered eligible for salvage irradiation of the scalp. We decided to use helical tomotherapy, which combines conformity of dose delivery with the possibility of daily control of the setup accuracy. Forty gray (2Gy/fraction) to the planning target volume and 50 Gy (2.5Gy/fraction) to the biological target volume defined on the basis of 18FDG-PET/CT was prescribed with a simultaneous integrated boost technique. After 12 fractions the patient was submitted to intermediate evaluation by 18FDG-PET/CT, which showed a partial response to the treatment. After 2, 4, 8, and 12 months, 18FDG-PET/CT showed a complete metabolic local response. This experience suggests a possible role of 18FDG-PET/CT-guided helical tomotherapy as an alternative to repeated and frequently demolitive surgery approaches.

Multi-site evaluation of the Razor stereotactic diode for CyberKnife small field relative dosimetry.

PURPOSE: The aims of this study were: (i) to validate in a multi-site context the suitability of the IBA Razor silicon diode detector for CyberKnife relative dosimetry. (ii) to fit the multi-center experimental data into a function relating the field output factors to the effective field size (EFS). METHODS AND MATERIALS: Ratio of detector readings in clinical and reference field (OFdet) and beam profiles were acquired on five CyberKnife units for fixed collimator diameters (range 5-60 mm), using both Razor and PTW 60017 diodes. Measured OFdet were corrected using published MonteCarlo correction factors to get field output factors ΩQclin,Qmsrfclin,fmsr. Profiles were analyzed in terms of penumbra and EFS. ΩQclin,Qmsrfclin,fmsr obtained in four centers were fitted as a function of EFS, while the data of the 5th center were used to validate the fitting curve. RESULTS: Differences between Razor and PTW60017 ΩQclin,Qmsrfclin,fmsr were within 1.5% over all centers down to 7.5 mm aperture and within 3.5% for the 5 mm diameter. The fit showed a coefficient of determination R2 = 0.997. The mean deviation of measured points from the predictive curve was within 0.5%. Data of the 5th center showed a mean deviation of 0.4% from the curve, with maximum differences within 2.5% for the 7.5 mm aperture. CONCLUSIONS: The results confirmed the suitability of Razor detector for CyberKnife dosimetry by comparison to the PTW 60017 diode which has been well characterized and is in widespread use. The proposed mathematical relation between ΩQclin,Qmsrfclin,fmsr and EFS is a robust predictive model applicable to different CyberKnife systems and detectors.

Adenoid cystic carcinoma of trachea treated with adjuvant hypofractionated tomotherapy. Case report and literature review.

Adenoid cystic carcinoma, also called cylindroma, is the second most common histological type of tracheal malignancy but represents 1% of all respiratory tract cancers. We report a case of a 59-year-old patient submitted to an incomplete resection of the trachea and subsequently treated with adjuvant tomotherapy. There have been no reports in the literature regarding intensity-modulated radiation therapy with linac or tomotherapy systems in adenoid cystic carcinoma of the trachea. The present clinical case demonstrates the feasibility of adjuvant intensity-modulated radiation therapy techniques for optimizing the dose coverage of the tumor bed while sparing surrounding normal tissues. A dosimetric comparison between the tomotherapy plan and a 3-dimensional conformal radiotherapy plan is also reported. We demonstrate that tomotherapy permits an increase in the dose per fraction without important acute adverse effects. At 24 months' follow-up, our patient shows no evidence of disease with negative histological findings.

Partial breast irradiation with CyberKnife after breast conserving surgery: a pilot study in early breast cancer.

BACKGROUND: Local recurrences after breast conserving treatment are mainly close to the original tumor site, and as such shorter fractionation strategies focused on and nearest mammary gland, i.e. accelerated partial breast irradiation (APBI), have been developed. Stereotactic APBI has been attempted, although there is little experience using CyberKnife (CK) for early breast cancer. METHODS: This pilot study was designed to assess the feasibility of CK-APBI on 20 evaluable patients of 29 eligible, followed for 2 years. The primary endpoint was acute/sub-acute toxicity; secondary endpoints were late toxicity and the cosmetic result. RESULTS: Mean pathological tumor size was 10.5 mm (±4.3, range 3-18), 8 of these patients were classified as LumA-like, 11 as LumB-like, and 1 as LumB-HER2-enriched. Using CK-APBI with Iris, the treatment time was approximately 60 min (range~ 35 to ~ 120). All patients received 30 Gy in five fractions delivered to the PTV. The median number of beams was 180 (IQR 107-213; range:56-325) with a median PTV isodose prescription of 86.0% (IQR 85.0-88.5; range:82-94). The median PTV was 88.1 cm3 (IQR 63.8-108.6; range:32.3-238.8). The median breast V100 and V50 was 0.6 (IQR 0.1-1.5; range:0-13) and 18.6 (IQR 13.1-21.7; range:7.5-37), respectively. The median PTV minimum dose was 26.2 Gy (IQR 24.7-27.6; range 22.3-29.3). Mild side effects were recorded during the period of observation. Cosmetic evaluations were performed by three observers from the start of radiotherapy up to 2 years. Patients' evaluation progressively increase from 60% to 85% of excellent rating; this trend was similar to that of external observer. CONCLUSIONS: These preliminary results showed the safe feasibility of CK-APBI in early breast cancer, with mild acute and late toxicity and very good cosmetic results. TRIAL REGISTRATION: The present study is registered at Clinicaltrial.gov ( NCT02896322 ). Retrospectively egistered August 4, 2016.

Agreement criteria between expected and measured field fluences in IMRT of head and neck cancer: the importance and use of the gamma histograms statistical analysis.

BACKGROUND AND PURPOSE: The aim of this study was to analyse our pre-treatment QA data in order to establish uniquely defined agreement criteria between planned and delivered dose distribution for clinical QA practice in IMRT of head and neck (HN) patients. MATERIALS AND METHODS: Pre-treatment QA dosimetry using films in combination with ionisation chambers is routinely evaluated for each patient. This evaluation is performed by comparing planned and measured dose distributions in terms of absolute point dose measurements, planar dose verification and gamma function analysis using 4%/3mm values as acceptance criteria. In the current investigation, gamma histograms, calculated on dose levels higher than 10% of the prescription dose (1.8Gy/fraction), were further analysed by considering mean values, gamma values corresponding to Delta=mean+1.5 SD (named as gamma(Delta)) and the % of points with gamma<1, gamma<1.5 and gamma>2. When considering the patient population, the average values of all these parameters and their confidence limits (mean value+1.5 SD) were calculated. The results here presented refer to 57 HN patients treated in the period September 04-April 06. RESULTS: Better results were found for treatments performed with our newly installed linac (e.g. average gamma(Delta): 0.8 vs. 1.1 for the preexisting one, p<0.001), due to a more accurate dosimetric configuration. Also, confidence limits for the percentage of points with gamma<1, gamma<1.5 and gamma>2 were found to be quite different for the two linacs (95.3%, 98.9% and 0.4% for the newly installed unit, 87.6%, 95.2% and 2.0% for the preexisting one). CONCLUSIONS: Statistical analyses of gamma evaluation of QA pre-treatment dosimetry are useful to properly define confidence limits of the agreement between expected and measured fluences based on our institutional experience. Our results confirm that the dosimetry configuration of the beam may significantly affect the agreement between planned and measured IMRT beam fluences.

Integration of Functional Magnetic Resonance Imaging and Magnetoencephalography Functional Maps Into a CyberKnife Planning System: Feasibility Study for Motor Activity Localization and Dose Planning.

OBJECTIVE: Magnetoencephalography (MEG) and functional magnetic resonance imaging (fMRI) provide noninvasive localization of eloquent brain areas for presurgical planning. The aim of this study is the integration of MEG and fMRI maps into a CyberKnife (CK) system to optimize dose planning. METHODS: Four patients with brain metastases in the motor area underwent functional imaging study of the hand motor cortex before radiosurgery. MEG data were acquired during a visually cued hand motor task. Motor activations were identified also using an fMRI block-designed paradigm. MEG and fMRI maps were then integrated into a CK system and contoured as organs at risk for treatment planning optimization. RESULTS: The integration of fMRI data into the CK system was achieved for all patients by means of a standardized protocol. We also implemented an ad hoc pipeline to convert the MEG signal into a DICOM standard, to make sure that it was readable by our CK treatment planning system. Inclusion of the activation areas into the optimization plan allowed the creation of treatment plans that reduced the irradiation of the motor cortex yet not affecting the brain peripheral dose. CONCLUSIONS: The availability of advanced neuroimaging techniques is playing an increasingly important role in radiosurgical planning strategy. We successfully imported MEG and fMRI activations into a CK system. This additional information can improve dose sparing of eloquent areas, allowing a more comprehensive investigation of the related dose-volume constraints that in theory could translate into a gain in tumor local control, and a reduction of neurological complications.

Significant improvement in normal tissue sparing and target coverage for head and neck cancer by means of helical tomotherapy.

PURPOSE: In order to explore the potential of helical Tomotherapy in the treatment of head and neck cancers (HNC), a planning study comparing our routinely delivered IMRT technique (dynamic MLC Varian 600CD Linac, inversely optimised by the Helios/Eclipse system) against two different Tomotherapy planning approaches was performed. MATERIALS AND METHODS: In the first Tomotherapy plan (TOMO-a), we merely applied the same constraints used for the IMRT-Linac technique; in the second one (TOMO-b), we tried to stress the sparing of parotids and mandible while keeping PTV coverage and spinal cord Dmax similar to their values in the TOMO-a plan. Five patients with locally advanced oropharinx (n=3), hypopharinx (n=1) and larynx (n=1) cancer were considered. For each patient, CTV1 including neck nodes and the tumour was defined and was expanded with a margin of 0.5 cm (PTV1); then, CTV2 including high risk nodes and CTV3 including only T were defined and the corresponding PTV2/PTV3 were defined by a 0.5 cm expansion. IMRT and Tomotherapy planning were optimised to deliver 54 Gy in 30 fractions on PTV1 and 16.2 Gy in 9 fractions on PTV3; in the case a PTV2 was defined, 15 Gy were concomitantly delivered while delivering 16.2 Gy on PTV3. Separated plans for the two phases (Phase 1: first 30 fractions; Phase 2: last 9 fractions) were compared in terms of dose-volume histograms (DVH) and dose statistics on PTVs and OARs. RESULTS: When considering Phase 1, Tomotherapy improved the homogeneity of the dose distribution within PTV1 while delivering the same prescribed dose (assessed to be the median dose to PTV): the fraction of PTV1 receiving more than 95% of the prescribed dose (V95%) increased from 90% (IMRT) to 96-97% for Tomotherapy plans. Dmax within PTV1 decreased from 60.3 Gy (IMRT) to 57.4 Gy (TOMO-a) and 58.7 Gy (TOMO-b). Spinal cord Dmax decreased from 31.6 Gy (IMRT) to 26.5 Gy (TOMO-a) and 24.6 Gy (TOMO-b). No attempts to further reduce spinal cord Dmax were done. Mean dose to the parotids decreased from 26.1 Gy (IMRT) to 25.1 Gy (TOMO-a) and 20.8 Gy (TOMO-b). Mandible was significantly better spared with Tomotherapy: mean dose decreased from 34.9 Gy (IMRT) to 34.0 Gy (TOMO-a) and 30.7 Gy (TOMO-b). When considering phase 2, the average gains (TOMO-b vs IMRT) were more modest and depended on the location of PTV2/PTV3. CONCLUSIONS: Preliminary findings obtained in a sequential approach for HNC suggest that Tomotherapy has the potential to significantly improve the therapeutic ratio with respect to a conventional IMRT delivery method.