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Purpose To classify COVID-19, COVID-19-like and non-COVID-19 interstitial pneumonia using lung CT radiomic features. Material and Methods CT data of 115 patients with respiratory symptoms suspected for COVID-19 disease were retrospectively analyzed. Based on the results of nasopharyngeal swab, patients were divided into two main groups, COVID-19 positive (C +) and COVID-19 negative (C−), respectively. C− patients, however, presented with interstitial lung involvement. A subgroup of C−, COVID-19-like (CL), were considered as highly suggestive of COVID pneumonia at CT. Radiomic features were extracted from the whole lungs. A dual machine learning (ML) model approach was used. The first one excluded CL patients from the training set, eventually included on the test set. The second model included the CL patients also in the training set. Results The first model classified C + and C− pneumonias with AUC of 0.83. CL median response (0.80) was more similar to C + (0.92) compared to C− (0.17). Radiomic footprints of CL were similar to the C + ones (possibly false negative swab test). The second model, however, merging C + with CL patients in the training set, showed a slight decrease in classification performance (AUC = 0.81). Conclusion Whole lung ML models based on radiomics can classify C + and C− interstitial pneumonia. This may help in the correct management of patients with clinical and radiological stigmata of COVID-19, however presenting with a negative swab test. CL pneumonia was similar to C + pneumonia, albeit with slightly different radiomic footprints.

Purpose Within the Italian Association of Medical Physics and Health Physics (AIFM) working group “FutuRuS” we carried out a survey regarding the number of the peer-reviewed articles by AIFM members. Methods We surveyed papers published in the years 2015–2019. Data extracted from Scopus included information regarding authors, title, journal, impact factor (IF), leading or standard authorship by AIFM members, keywords, type of collaboration (monocentric/multicentric/international), area of interest [radiation oncology (RO), radiology (RAD), nuclear medicine (NM), radioprotection (RP) and professional issue (PI)] and topics. Results We found 1210 papers published in peer-reviewed journals: 48%, 22%, 16%, 6%, 2 and 6% in RO, RAD, NM, RP, PI and other topics, respectively. Forty-seven percent of the papers involved monocentric teams, 31% multicentric and 22% international collaborations. Leading authorship of AIFM members was in 56% of papers, with a corresponding IF equal to 52% of the total IF (3342, IFmean = 2.8, IFmax = 35.4). The most represented journal was Physica Medica, with 15% of papers, while a relevant fraction of IF (54%) appeared in clinically oriented journals. The number of papers increased significantly between 2015 and 2016 and remained almost constant in 2017–2019. Conclusions This survey led to the first quantitative assessment of the number and theme distribution of peer-reviewed scientific articles contributed by AIFM members. It constitutes a ground basis to support future AIFM strategies and promote working groups on scientific activity of medical physicists, and to build the basis for rational comparison with other countries, first of all within Europe.

Background and ObjectiveTo assess the dosimetric feasibility of a stereotactic body radiotherapy (SBRT) dose escalated protocol, with a simultaneous integrated boost (SIB) and a simultaneous integrated protection (SIP) approach, in patients with locally advanced pancreatic cancer (LAPC).Material and MethodsTwenty LAPC lesions, previously treated with SBRT at our Institution, were re-planned. The original prescribed and administered dose was 50/30/25 Gy in five fractions to PTVsib (tumor-vessel interface [TVI])/PTVt (tumor volume)/PTVsip (overlap area between PTVt and planning organs at risk volume [PRVoars]), respectively. At re-planning, the prescribed dose was escalated up to 60/40/33 Gy in five fractions to PTVsib/PTVt/PTVsip, respectively. All plans were performed using an inspiration breath hold (IBH) technique and generated with volumetric modulated arc therapy (VMAT). Well-established and accepted OAR dose constraints were used (D0.5cc < 33 Gy for luminal OARs and D0.5cc < 38 Gy for corresponding PRVoars). The primary end-point was to achieve a median dose equal to the prescription dose for the PTVsib with D98≥ 95% (95% of prescription dose is the minimum dose), and a coverage for PTVt and PTVsip of D95≥95%, with minor deviations in OAR dose constraints in < 10% of the plans.ResultsPTVsib median (± SD) dose/D95/conformity index (CI) were 60.54 (± 0.85) Gy/58.96 (± 0.86) Gy/0.99 (± 0.01), respectively; whilst PTVt median (± SD) dose/D95 were 44.51 (± 2.69) Gy/38.44 (± 0.82) Gy, and PTVsip median (± SD) dose/D95 were 35.18 (± 1.42) Gy/33.01 (± 0.84) Gy, respectively. With regard to OARs, median (± SD) maximum dose (D0.5cc) to duodenum/stomach/bowel was 29.31 (± 5.72) Gy/25.29 (± 6.90) Gy/27.03 (± 5.67) Gy, respectively. A minor acceptable deviation was found for a single plan (bowel and duodenum D0.5cc=34.8 Gy). V38 < 0.5 cc was achieved for all PRV luminal OARs.ConclusionsIn LAPC patients SBRT, with a SIB/SIP dose escalation approach up to 60/40/33 Gy in five fractions to PTVsib/PTVt/PTVsip, respectively, is dosimetrically feasible with adequate PTVs coverage and respect for OAR dose constraints.

Background and ObjectiveThe aim of this study was to assess the ability of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) to provide functional information useful in predicting pathological response to an intensive neoadjuvant chemo-radiotherapy (nCRT) protocol for both esophageal squamous cell carcinoma (SCC) and adenocarcinoma (ADC) patients.Material and MethodsEsophageal carcinoma (EC) patients, treated in our Center between 2014 and 2018, were retrospectively reviewed. The nCRT protocol schedule consisted of an induction phase of weekly administered docetaxel, cisplatin, and 5-fluorouracil (TCF) for 3 weeks, followed by a concomitant phase of weekly TCF for 5 weeks with concurrent radiotherapy (50–50.4 Gy in 25–28 fractions). Three 18F-FDG PET/CT scans were performed: before (PET1) and after (PET2) induction chemotherapy (IC), and prior to surgery (PET3). Correlation between PET parameters [maximum and mean standardized uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)], radiomic features and tumor regression grade (TGR) was investigated.ResultsFifty-four patients (35 ADC, 19 SCC; 48 cT3/4; 52 cN+) were eligible for the analysis. Pathological response to nCRT was classified as major (TRG1-2, 41/54, 75.9%) or non-response (TRG3-4, 13/54, 24.1%). A major response was statistically correlated with SCC subtype (p = 0.02) and smaller tumor length (p = 0.03). MTV and TLG measured prior to IC (PET1) were correlated to TRG1-2 response (p = 0.02 and p = 0.02, respectively). After IC (PET2), SUVmean and TLG correlated with major response (p = 0.03 and p = 0.04, respectively). No significance was detected when relative changes of metabolic parameters between PET1 and PET2 were evaluated. At textural quantitative analysis, three independent radiomic features extracted from PET1 images ([JointEnergy and InverseDifferenceNormalized of GLCM and LowGrayLevelZoneEmphasis of GLSZM) were statistically correlated with major response (p < 0.0002).Conclusions18F-FDG PET/CT traditional metrics and textural features seem to predict pathologic response (TRG) in EC patients treated with induction chemotherapy followed by neoadjuvant chemo-radiotherapy. Further investigations are necessary in order to obtain a reliable predictive model to be used in the clinical practice.

Objectives To test whether 3 T multiparametric magnetic resonance imaging (mMRI) provides information related to molecular subtypes of breast cancer. Methods Women with mammographic or US findings of breast lesions (BI-RADS 4–5) underwent 3 T mMRI (DCE, DWI and MR spectroscopy). The histological type of breast cancer was assessed. Estrogen-receptor (ER), progesterone-receptor (PgR), Ki-67 status and HER-2 expression, assessed by immunohistochemistry (IHC), defined four molecular subtypes: Luminal-A, Luminal-B, HER2-enriched and triple-negative. Non-parametric tests (Kruskal-Wallis, k-sample equality of medians, and Mann-Whitney), logistic regression or ANOVA, and a multivariate analysis were performed to investigate correlations between the four molecular subtypes and mMRI (lesion volume, margins or distribution, enhancement pattern, ADC, type of kinetic curve, and total choline (tCho) signal-to-noise-ratio (SNR)). A ROC analysis was finally performed to test the diagnostic power of a multivariate logistic regression model. Results 433 patients (453 lesions) were considered. Volume was smaller in Luminal-B and larger in triple-negative tumours compared to the other subtypes combined. Margins were significantly correlated to Luminal-A and Luminal-B. The type of curve was significantly correlated to Luminal-A. ADC values were higher in Luminal-A. tCho SNR was higher in triple-negative tumours. The ROC analysis showed that the area under the curve (AUC) significantly improved when multiple MRI features were used compared to individual parameters. Conclusions A significant correlation was found between some MRI features and molecular subtypes of breast tumours. A multiparametric approach improved the diagnostic power of MRI. However, further research is needed in order to predict the molecular subtype on the sole basis of mMRI.

Purpose: To find an optimized workflow for the use of respiratory‐gated PET (4D‐PET) in target volume delineation of tumors subject to respiratory‐gated radiation therapy.Methods: 15 patients with lung (11) and pancreas (4) tumors who had FDG‐PET‐CT for target delineation prior to EBRT were studied. Patients were selected among the group that showed respiratory‐induced tumor motion 〉5mm. 4D‐PET was performed by means of a Philips Gemini BigBore scanner, using the Varian RPM gating system. An identical system was available at the linac for treatment. The breathing cycle was equally divided in 4 phases, according to a previous study. Since planning was made on a single CT‐phase, no ITV was explicitly built from the set of phases. The BTV was identified with SUV=2.2 threshold and the PTV was obtained expanding the BTV by 8mm(S‐I), 5mm(A‐P) and 3mm(L‐R) to account for residual motion and setup errors. The most advantageous CT‐phase for treatment planning was then identified by simulating plans on each phase and analyzing the resulting DVHs of OARs (lung, trachea, oesophagus, spinal cord, left ventricle). Results: The observed maximum range of motion was 5.5mm(L‐R), 12.3mm(A‐P) and 19.2mm(S‐I). The standard deviation of the BTV volume in the 4 phases ranged from 6% to 13.7%. V20 (lung) ranged 7.1%–15.2% in inspiration and 7.8%–18.6% in expiration. The mean dose to the oesophagus ranged 0.1–2.2Gy in inspiration and 1.4–2.0Gy in expiration. In general, the dose to OARs was smaller when planning on a single phase than on the overall, respiratory‐uncontrolled volume (p‐value〈0.05). Conclusions: The BTV volume was almost constant between phases, confirming that the motion might be described by 4 phases. There was no obvious choice of the optimal phase for treatment planning, suggesting patient‐by‐patient studies. However, planning and delivery on one phase consistently allowed dose sparing to be obtained compared to non‐gated techniques.

To test 3T proton magnetic resonance spectroscopy (1H-MRS) for breast mass lesions. Patients with BI-RADS 4–5 lesions at mammography/ultrasound were prospectively enrolled. After contrast-enhanced breast MRI, single-voxel MRS (point-resolved volume selection, PRESS); pencil-beam shimming; volume of interest 1 cm3; TR/TE = 3000/135 ms) was performed. Spectra were considered reliable if the full width at half maximum (FWHM) of the water peak was ≤45 Hz. A signal-to-noise ratio of the total choline (tCho) peak at 3.21 ppm ≥2 was used as cutoff for malignancy. All lesions underwent needle sampling. Final pathology was available for all malignant lesions; for benign lesions the reference standard was final pathology or at least 1-year negative follow-up. Reliable spectra were obtained in 115/127 lesions (91%), with a mean FWHM of 32.4 Hz (range 8–45 Hz). A tCho peak SNR ≥2 was detected in 66 malignant lesions (62 invasive cancers; 4 ductal carcinoma in situ) and in 3 benign lesions. Excluding lesions located ≤1 cm from the skin (n = 3) or pectoral muscle (n = 11), sensitivity was 65/73 [89%, 95% confidence interval (CI): 80–95%], and specificity 25/28 (89%) (95% CI: 72–98%). Considering only invasive cancers, sensitivity reached 61/68 (90%, 95% CI: 81–96%). MRS additional time was 8 min. When lesions close to the skin or pectoral muscle are excluded, 3T 1H-MRS of mass lesions ≥1 cm showed a high diagnostic performance, however, insufficient to avoid needle biopsy.

To test a single-energy low-voltage CT protocol for pancreatic adenocarcinoma.A total of 30 patients with pathology-proven pancreatic adenocarcinoma underwent 64-row MDCT with arterial phase at 80 kV and were compared to a similar group of 30 patients scanned with a 120 kV protocol. Scans were compared for quantitative image parameters (attenuation and standard deviation in the pancreas, tumor, aorta), CTDI and DLP using an unpaired t-test. Image noise values for each protocol (SD of the psoas) were compared using an unpaired t-test. Effective dose was calculated for each protocol. CNR (=conspicuity/SDnoise) and FOM (CNR2/ED) were calculated. The Catphan600 phantom was used to evaluate image non-uniformity, noise, spatial resolution, and low contrast detectability.Mean patient weight was 68 kg in the study group and 73 kg in the control group (p=0.0355), while patient diameters at the celiac axis were not significantly different. Mean attenuation was significantly higher at 80 kV in the aorta (517.5±116.4 vs 290.3±76.4 HU) and normal pancreas (154.0±39.95 vs 90.02±19.01 HU) (all p0.0001), while no significant difference was observed for adenocarcinoma (61.43±35.61 vs 47.45±18.95; p=n.s.). CTDI and DLP were significantly lower at 80 kV (6.00±0.90 mGy vs 10.24±2.93 mGy, and 180.4±35.49 mGy cm vs 383.8±117 mGy cm, respectively; all p0.0001). Tumor conspicuity (HUpancreas-HUtumor) was significantly higher at 80 kV (94.2±39.3 vs 39.5±22 HU; p0.0001). Mean image noise was significantly higher at 80kV (28.32±10.06 vs 19.7±7.1HU; p0.0001). Effective dose was significantly lower at 80 kV (1.984±0.39 vs 5.75±1.75 mSv; p0.0001). The total DLP for the exam was 1024±31.86 mGy cm for the 80 kV protocol and 1357±62.60 mGy cm for the 120 kV protocol (p0.0001). Phantoms showed higher non-uniformity, slightly higher noise, slightly lower MTF (50%) and slightly higher percentage contrast for the 80 kV protocol.Single-source 80 kV pancreatic phase scanning results in higher conspicuity of pancreatic adenocarcinoma and FOM and in significant dose reduction while maintaining acceptable image quality.

Introduction The aim of this work was to assess the role of 3T-MR spectroscopy (MRS) in the multi-parametric MRI evaluation of breast lesions, using a pattern-recognition based classification method. Methods 291 patients (301 lesions, median 2.3 cm3) were enrolled in the study (age 18–85 y, mean 54.2 y). T1-TSE (TR/TE = 400/10 ms) and T2-STIR imaging (TR/TE = 5000/60 ms), dynamic-contrast-enhanced MRI (DCE-MRI), apparent diffusion coefficient (ADC) (b = 0–800 s/mm2), and single-voxel MRS (10 × 10 × 10 mm3, PRESS, TR/TE = 3000 ms/135 ms) were performed by means of a 3T scanner. MRS results were accepted if the FWHM of the water peak was ⩽45 Hz. Total choline (tCho) was considered detected if the signal-to-noise ratio (SNR) of the 3.2 ppm peak was ⩾2. A classifier-based analysis (support-vector-machines, SVM) was performed with 4-dimensional vectors including type of margin, DCE-MRI kinetic curve type, ADC mean value, and tCho SNR. A comparison with 3-dimensional vectors (without tCho SNR) was used to assess MRS impact on sensitivity, specificity, and positive-negative predictive values (PPV-NPV) for malignancy. Results 228 lesions (180 malignant/48 benign) showed acceptable spectral quality. Comparison of classification results with histopathological examination of surgical specimens showed sensitivity = 93.7%, specificity = 84.9%, PPV = 95.2%, NPV = 81.5% without the inclusion of MRS in the SVM analysis. When MRS was included, the figures increased to 95.1%, 90.7%, 97.2%, and 85.0%, respectively. Conclusions Inclusion of 3T-MRS in the multi-parametric MRI evaluation of breast lesions improved the performance of the SVM-based classifier, showing a possible role of high-field MR spectroscopy in the differential diagnosis between benign and malignant breast lesions. Further research is however needed to confirm this initial evidence.

The aim of this work was to investigate the main dosimetric characteristics and the performance of an A26 Exradin ionization microchamber (A26 IC) and a W1 Exradin plastic scintillation detector (W1 PSD) in small photon beam dosimetry for treatment planning system commissioning and quality assurance programme.Detector characterization measurements (short-term stability, dose linearity, angular dependence and energy dependence) were performed in water for field sizes up to 10 × 10 cmResults were compared with those obtained with other detectors we already use for small photon beam dosimetry. A26 IC and W1 PSD showed a linear dose response. While the A26 IC showed no energy dependence, the W1 PSD showed energy dependence within 2%; no angular dependence was registered. PThe results of our investigation confirm that A26 IC and W1 PSD could play an important role in small field relative dosimetry. Advances in knowledge: Dosimetric characteristics of Exradin A26 ionization microchamber and W1 plastic scintillation detector for small field dosimetry.

Purpose: In highly-conformal radiotherapy, due to the complexity of both beam configurations and dose distributions, traditional in vivo dosimetry is unpractical or even impossible. The ideal dosimeter would be implanted inside the planning treatment volume so that it can directly measure the total delivered dose during each fraction with no additional uncertainty due to calculation models. The aim of this work is to verify if implantable metal oxide semiconductors field effect transistors (MOSFETs) can achieve a sufficient degree of dosimetric accuracy when used inside extracranial targets undergoing radiotherapy treatments using the Cyberknife system. Methods: Based on the preliminary findings of this study, new prototypes for high dose fractionations were developed to reduce the time dependence for long treatment delivery times. These dosimeters were recently cleared and are marketed as DVS-HFT. Multiple measurements were performed using both Virtual Water and water phantoms to characterize implantable MOSFETs under the Cyberknife beams, and included the reference-dosimetry consistency, the dependence of the response on the collimator size, on the daily delivered dose, and the time irradiation modality. Finally a Cyberknife prostate treatment simulation using a body phantom was conducted, and both MOSFET and ionization readings were compared to Monte Carlo calculations. The feasibility analysismore » was conducted based on the ratios of the absorbed dose divided by the dose reading, named as ''further calibration factor'' (FCF). Results: The average FCFs resulted to be 0.98 for the collimator dependence test, and about 1.00 for the reference-dosimetry test, the dose-dependence test, and the time-dependence test. The average FCF of the prostate treatment simulation test was 0.99. Conclusions: The obtained results are well within DVS specifications, that is, the factory calibration is still valid for such kind of treatments using the Cyberknife system, with no need of further calibration factors to be applied. The final accuracy of implantable MOSFETs when used for such kind of treatments was estimated to be within {+-}4%. Additional investigations using dose/fraction higher than 12 Gy, different beam configurations, and tracking systems could extend the present findings to other kind of treatments. MOSFET technology was proven to have high versatility in fast adaptation of existing detectors to new applications. It is plausible to expect a general feasibility of implantable MOSFET technology for in vivo dosimetry of the extracranial-targets treatments using the Cyberknife, provided each particular application will be validated by suitable both physical and clinical studies.« less

Object The authors describe a method that utilizes an image-guided robotic radiosurgical apparatus (the CyberKnife) for treatment of cerebral arteriovenous malformations (AVMs). This procedure required the development of an original technique that allows a high degree of automation. Methods Angiographic images were imported into the treatment planning software by coregistering CT and 3D rotational angiography. The nidus contour was delineated using the contouring tools of the treatment planning system. Functional MR imaging was employed for contouring critical cortical regions, such as the motor cortex and language areas. Once the radiation dose to be delivered to the target volume and dose constraints to critical structures were prescribed, the inverse treatment planning function determined the optimal treatment plan. Results A series of 279 patients with cerebral AVMs underwent CyberKnife radiosurgery. One transitory adverse effect of the radiation procedure was observed. Eight bleeding occurrences were noted before complete AVM obliteration. Of the 102 patients with follow-up > 36 months, 80 underwent angiographic evaluation. In this group, 65 patients (81.2%) showed complete angiographic obliteration of their AVM. In 8 more patients, complete angiographic obliteration was demonstrated by MR angiography only. Conclusions This is the first report describing a technique developed for CyberKnife radiosurgery of cerebral AVMs. The use of different imaging modalities for automatic delineation of the target and critical structures combined with the employment of the inverse treatment planning capability is the crucial point of the procedure. The procedure proved to be safe and efficient.

Purpose An analysis is performed of the setup errors measured by a kV cone beam computed tomography (CBCT) for intracranial stereotactic radiotherapy (SRT) patients immobilized by a thermoplastic mask and a bite-block and positioned using stereotactic coordinates. We evaluated the overall positioning precision and accuracy of the immobilizing and localizing systems. The potential of image-guided radiotherapy to replace stereotactic methods is discussed. Methods and Materials Fifty-seven patients received brain SRT. After a frame-guided setup, before each fraction (131 fractions), a CBCT was acquired and the detected displacements corrected online. Translational and rotational errors were analyzed calculating overall mean and standard deviation. A separate analysis was performed for bite-block (in conjunction with mask) and for simple thermoplastic mask. Interobserver variability for CBCT three-dimensional registration was assessed. The residual error after correction and intrafractional motion were calculated. Results The mean module of the three-dimensional displacement vector was 3.0 ± 1.4 mm. Setup errors for bite block and mask were smaller (2.9 ± 1.3 mm) than those for thermoplastic mask alone (3.2 ± 1.5 mm), but statistical significance was not reached ( p = 0.15). Interobserver variability was negligible. The maximum margin calculated for residual errors and intra fraction motion was small but not negligible (1.57 mm). Conclusions Considering the detected setup errors, daily image guidance is essential for the efficacy of SRT treatments when mask immobilization is used, and even when a bite-block is used in conjunction. The frame setup is still used as a starting point for the opportunity of rotational corrections. Residual margins after on-line corrections must be evaluated.

Purpose Different biologically equivalent dose (BED) values associated with stereotactic radiotherapy (SRT) of patients with primary and metastatic pulmonary nodules were studied. The BED values were calculated for tumoral tissue and low α/β ratio, assuming that better local response could be obtained by using stereotactic high-BED treatment. Methods and Materials Fifty-eight patients with T1–T3 N0 non–small-cell lung cancer and 46 patients with metastatic lung nodules were treated with SRT. The BED was calculated for α/β ratios of 3 and 10. Overall survival (OS) was assessed according to Kaplan-Meier and appraised as a function of three BED levels: low (30–50 Gy), medium (50–70 Gy), and high (70–98 Gy; α/β = 10). Results The OS rates for all 104 patients at 12, 24, and 36 months were 73%, 48.3%, and 35.8%, respectively. Local response greater than 50% for low, medium, and high BED values was observed in 54%, 47%, and 73%, respectively. In the high-BED treated group, OS rates at 12, 24, and 36 months (80.9%, 70%, and 53.6%, respectively) were significantly improved compared with low- (69%, 46.1%, and 30.7%, respectively) and medium-BED (67%, 28%, and 21%, respectively) treated patients. Results are also discussed in terms of BED calculated on α/β 3 Gy characteristic of the microcapillary bed. No acute toxicity higher than Grade 1 was observed. Conclusions Radioablation of pulmonary neoplastic nodules may be achieved with SRT delivered by using a high-dose fraction with high BED value.

Functional magnetic resonance imaging (fMRI) is used to distinguish areas of the brain responsible for different tasks and functions. It is possible, for example, by using fMRI images, to identify particular regions in the brain which can be considered as "functional organs at risk" (fOARs), i.e., regions which would cause significant patient morbidity if compromised. The aim of this study is to propose and validate a method to exploit functional information for the identification of fOARs in CyberKnife (Accuray, Inc., Sunnyvale, CA) radiosurgery treatment planning; in particular, given the high spatial accuracy offered by the CyberKnife system, local nonrigid registration is used to reach accurate image matching. Five patients affected by arteriovenous malformations (AVMs) and scheduled to undergo radiosurgery were scanned prior to treatment using computed tomography (CT), three-dimensional (3D) rotational angiography (3DRA), T2 weighted and blood oxygenation level dependent echo planar imaging MRI. Tasks were chosen on the basis of lesion location by considering those areas which could be potentially close to treatment targets. Functional data were superimposed on 3DRA and CT used for treatment planning. The procedure for the localization of fMRI areas was validated by direct cortical stimulation on 38 AVM and tumor patients undergoing conventional surgery. Treatment plans studied with and without considering fOARs were significantly different, in particular with respect to both maximum dose and dose volume histograms; consideration of the fOARs allowed quality indices of treatment plans to remain almost constant or to improve in four out of five cases compared to plans with no consideration of fOARs. In conclusion, the presented method provides an accurate tool for the integration of functional information into AVM radiosurgery, which might help to minimize undesirable side effects and to make radiosurgery less invasive.

The inclusion of organ deformation and movement in radiosurgery treatment planning is of increasing importance as research and clinical applications begin to take into consideration the effects of physiological processes, like breathing, on the shape and position of lesions. In this scenario, the challenge is to localize the target in toto (not only by means of marker sampling) and to calculate the dose distribution as the sum of all the contributions from the positions assumed by the target during the respiratory cycle. The aim of this work is to investigate the use of nonrigid registration for target tracking and dynamic treatment planning, i.e., treatment planning based not on one single CT scan but on multiple CT scans representative of the respiration. Twenty patients were CT scanned at end-inhale and end-exhale. An expert radiation oncologist identified the PTV in both examinations. The two CT data sets per patient were nonrigidly registered using a free-form deformation algorithm based on B-splines. The optimized objective function consisted of a weighted sum of a similarity criterion (Mutual Information) and a regularization factor which constrains the transformation to be locally rigid. Once the transformation was obtained and the registration validated, its parameters were applied to the target only. Finally, the deformed target was compared to the PTV delineated by the radiation oncologist in the other study. The results of this procedure show an agreement between the center of mass as well as volume of the target identified automatically by deformable registration and manually by the radiation oncologist. Moreover, obtained displacements were in agreement with body structure constraints and considerations usually accepted in radiation therapy practice. No significant influence of initial target volume on displacements was found. In conclusion, the proposed method seems to offer the possibility of using nonrigid registrations in radiosurgery treatment planning, even if more cases need to be investigated in order to give a statistical consistency to parameter setup and proposed considerations.

In this paper a novel technique is proposed and validated for radiosurgery treatment planning of arteriovenous malformations (AVMs). The technique was developed for frameless radiosurgery by means of the CyberKnife, a nonisocentric, linac-based system which allows highly conformed isodose surfaces to be obtained, while also being valid for other treatment strategies. The technique is based on registration between computed tomography (CT) and three-dimensional rotational angiography (3DRA). Tests were initially performed on the effectiveness of the correction method for distortion offered by the angiographic system. These results determined the registration technique that was ultimately chosen. For CT-3DRA registration, a twelve-parameter affine transformation was selected, based on a mutual information maximization algorithm. The robustness of the algorithm was tested by attempting to register data sets increasingly distant from each other, both in translation and rotation. Registration accuracy was estimated by means of the "full circle consistency test." A registration quality index (expressed in millimeters) based on these results was also defined. A hybrid subtraction between CT and 3DRA is proposed in order to improve 3D reconstruction. Preprocessing improved the ability of the algorithm to find an acceptable solution to the registration process. The robustness tests showed that data sets must be manually prealigned within approximately 15 mm and 20 degrees with respect to all three directions simultaneously. Results of the consistency test showed agreement between the quality index and registration accuracy stated by visual inspection in 20 good and 10 artificially worsened registration processes. The quality index showed values smaller than the maximum voxel size (mean 0.8 mm compared to 2 mm) for all successful registrations, while it resulted in much greater values (mean 20 mm) for unsuccessful registrations. Once registered, the two data sets can be used for CyberKnife treatment planning. Target delineation is performed on 3DRA while dose calculation and DRR generation are performed on CT. In conclusion, a method was developed for using 3DRA images for AVM frameless radiosurgery treatment planning. The method proved to be feasible, robust, and accurate for clinical use. 3DRA can be performed at different times or locations compared to standard, frame based stereotactic angiography. Unlike two-dimensional angiography, 3DRA allows examination of the shape of the AVM and of the surrounding target from any arbitrary point of view during treatment planning. The method can be applied to any case of intermodality registration, is operator-independent, and allows estimation of registration quality. Further research is desirable to improve time resolution in order to distinguish between feeding and draining vessels.

Object. Radiosurgical treatment of a cerebral arteriovenous malformation (AVM) requires the precise definition of the nidus of the lesion in stereotactic space. This cannot be accomplished using simple stereotactic angiography, but requires a combination of stereotactic biplanar angiographic images and stereotactic contrast-enhanced computerized tomography (CT) scans. In the present study the authors describe a method in which three-dimensional (3D) rotational angiography is integrated into stereotactic space to aid treatment planning for radiosurgery. Methods. Twenty patients harboring AVMs underwent treatment planning prior to linear accelerator radiosurgery. Planning involved the acquisition of two different data sets, one of which was obtained using the standard method (a combination of biplanar stereotactic angiography with stereotactic CT scanning), and the other, which was procured using a new technique (nonstereotactic 3D rotational angiography combined with stereotactic CT scanning by a procedure of image fusion). The treatment plan that was developed using the new method was compared with that developed using the standard one. For each patient the number of isocenters and the dimension of selected collimators were the same, based on the information supplied in both methods. Target coordinates were modified in only five cases and by a limited amount (mean 0.7 mm, range 0.3–1 mm). Conclusions. The new imaging modality offers an easier and more immediate interpretation of 3D data, while maintaining the same accuracy in target definition as that provided by the standard technique. Moreover, the new method has the advantage of using nonstereotactic 3D angiography, which can be performed at a different site and a different time with respect to the irradiation procedure.

The purpose of the study is to evaluate the performance of a novel strategy, referred to as “virtual 4D PET”, aiming at the optimization of hybrid 4D CT-PET scan for radiotherapy treatment planning. The virtual 4D PET strategy applies 4D CT motion modeling to avoid time-resolved PET image acquisition. This leads to a reduction of radioactive tracer administered to the patient and to a total acquisition time comparable to free-breathing PET studies. The proposed method exploits a motion model derived from 4D CT, which is applied to the free-breathing PET to recover respiratory motion and motion blur. The free-breathing PET is warped according to the motion model, in order to generate the virtual 4D PET. The virtual 4D PET strategy was tested on images obtained from a 4D computational anthropomorphic phantom. The performance was compared to conventional motion compensated 4D PET. Tests were also carried out on clinical 4D CT-PET scans coming from seven lung and liver cancer patients. The virtual 4D PET strategy was able to recover lesion motion, with comparable performance with respect to the motion compensated 4D PET. The compensation of the activity blurring due to motion was successfully achieved in terms of spill out removal. Specific limitations were highlighted in terms of partial volume compensation. Results on clinical 4D CT-PET scans confirmed the efficacy in 4D PET count statistics optimization, as equal to the free-breathing PET, and recovery of lesion motion. Compared to conventional motion compensation strategies that explicitly require 4D PET imaging, the virtual 4D PET strategy reduces clinical workload and computational costs, resulting in significant advantages for radiotherapy treatment planning.

Purpose: A simple method that verifies the coincidence of the isocenter with the center of the target volume in radiosurgery treatment conditions is described. The accuracy is compared to that of accepted computerized procedures employing fiducial markers. Methods and Materials: The center of the beam is identified by a cylindrical localizer, fixed to the plate of the supplemental collimator, with a 2 × 50 mm tungsten rod coincident with the beam axis and is projected onto the x-ray portal verification films. Prior to irradiation, the coordinates of the intersection of the beams axes, which is in a known spatial relationship with the isocenter, are read directly on portal x-ray films and their coincidence with the coordinates set during patient positioning, is checked. Results: The mean displacement in AP, Lat, and Vert coordinates respectively, over 84 patients, between the coordinates calculated by the computerized procedure employing fiducial markers and the coordinates calculated by using the rulers was 0.3 ± 0.4 mm. Conclusions: From the results obtained with the two methods we can conclude that rulers method can be used as a fast indirect control of the position of the radiation isocenter. Moreover, the dimensions of the radiation field and the correct alignment of the tertiary circular collimator can be also documented.

Objective To present initial, short-term results obtained with an image-guided radiosurgery apparatus (CyberKnife; Accuray, Inc., Sunnyvale, CA) in a series of 199 benign intracranial meningiomas. Methods Selection criteria included lesions unsuitable for surgery and/or remnants after partial surgical removal. All patients were either symptomatic and/or harboring growing tumors. Ninety-nine tumors involved the cavernous sinus; 28 were in the posterior fossa, petrous bone, or clivus; and 29 were in contact with anterior optic pathways. Twenty-two tumors involved the convexity, and 21 involved the falx or tentorium. One hundred fourteen patients had undergone some kind of surgical removal before radiosurgery. Tumor volumes varied from 0.1 to 64 mL (mean, 7.5 mL) and radiation doses ranged from 12 to 25 Gy (mean, 18.5 Gy). Treatment isodoses varied from 70 to 90%. In 150 patients with lesions larger than 8 mL and/or with tumors situated close to critical structures, the dose was delivered in 2 to 5 daily fractions. Results The follow-up periods ranged from 1 to 59 months (mean, 30 months; median, 30 months). The tumor volume decreased in 36 patients, was unchanged in 148 patients, and increased in 7 patients. Three patients underwent repeated radiosurgery, and 4 underwent operations. One hundred fifty-four patients were clinically stable. In 30 patients, a significant improvement of clinical symptoms was obtained. In 7 patients, neurological deterioration was observed (new cranial deficits in 2, worsened diplopia in 2, visual field reduction in 2, and worsened headache in 2). Conclusion The introduction of the CyberKnife extended the indication to 63 patients (>30%) who could not have been treated by single-session radiosurgical techniques. The procedure proved to be safe. Clinical improvement seems to be more frequently observed with the CyberKnife than in our previous linear accelerator experience.

Spatial accuracy in extracranial radiosurgery is affected by organ motion. Motion tracking systems may be able to avoid PTV enlargement while preserving treatment times, however special attention is needed when fiducial markers are used to identify the target can move with respect to organs at risk (OARs). Ten patients treated by means of the Synchrony system were taken into account. Sparing of irradiated volume and of complication probability were estimated by calculating treatment plans with a motion tracking system (Cyberknife Synchrony, Sunnyvale, CA, USA) and a PTV-enlargement strategy for ten patients. Six patients were also evaluated for possible inaccuracy of estimation of dose to OARs due to relative movement between PTV and OAR during respiration. Dose volume histograms (DVH) and Equivalent Uniform Dose (EUD) were calculated for the organs at risk. In the cases for which the target moved closer to the OAR (three cases of six), a small but significant increase was detected in the DVH and EUD of the OAR. In three other cases no significant variation was detected. Mean reduction in PTV volume was 38% for liver cases, 44% for lung cases and 8.5% for pancreas cases. NTCP for liver reduced from 23.1 to 14.5% on average, for lung it reduced from 2.5 to 0.1% on average. Significant uncertainty may arise from the use of a motion-tracking device in determination of dose to organs at risk due to the relative motion between PTV and OAR. However, it is possible to limit this uncertainty. The breathing phase in which the OAR is closer to the PTV should be selected for planning. A full understanding of the dose distribution would only be possible by means of a complete 4D-CT representation.

The purpose of this study was to evaluate the results of interstitial radiosurgery (IR) with Photon Radiosurgery System (PRS) in 18 patients (P) with deep-seated brain primary or secondary tumors. Follow-up varied from 2 to 53 months (mean, 13.6 mo). Seven P with glioblastomas died due to tumor progression. Five P with metastases died for systemic disease while local control was achieved in all. Six P with low-grade astrocytomas were well and imaging showed tumor control. We conclude that PRS IR is effective in the treatment of metastases while it provides lower benefit in malignant gliomas. It could play a major role in low-grade astrocytomas.

The purpose of this work is to compare the photon dose calculation of a commercially available three-dimensional (3D) treatment planning system based on the collapsed cone convolution technique against BEAM, a Monte Carlo code that allows detailed simulation of a radiotherapy accelerator. The first part of the work is devoted to the commissioning of BEAM for a 6 MV photon beam and to the optimization of the linac description to fit the experimental data. This step also involves a comparison with radiochromic film data on an inhomogeneous phantom built to simulate electronic nonequilibrium conditions. Commissioning the selected photon beams required a careful description of the treatment head and the fine tuning of physical parameters such as electron beam energy and radius. The second part shows the dose comparison for real patient's CT data sets: A mediastinal treatment and a breast treatment were simulated. Doses in terms of absolute values per monitor unit were calculated based on the BEAM simulation of the CT data sets. For comparisons of real-patient cases, differences between the treatment planning system and BEAM ranged from 0 to 2.6% and were within +/-2 standard deviations for the dose calculated at the prescription point. Dose-volume histogram analysis indicated that there is no consistent difference between the Monte Carlo and the convolution calculations. On the basis of the results presented in this study, we can conclude that the CCC algorithm is capable of giving results absolutely comparable to those of a Monte Carlo calculation, as far as common 3D radiotherapy planning is concerned.

Purpose: To compare Extracranial Radiosurgerydose distributions to step and shoot Intensity Modulated Radiation Therapy(IMRT) aimed to the same dose prescriptions and constraints. Method and Materials: 12 patients treated by means of the Cyberknife system for extracranial tumors (7 lung, 2 pancreas, 2 liver and 1 prostate) were selected. Volume of the PTV ranged from 19.0 cc to 584.4 cc. The prescribed doses were 16–27 Gy to the 80% isodose surface in 1–3 fractions. IMRTtreatment plans were calculated to obtain the same coverage of the PTV with same constraints to organs at risk. A 5‐coplanar fields, step‐and‐shoot technique was employed with a 6MV accelerator. IMRT plans were generated by means of the Pinnacle treatment planning system. We compared homogeneity and conformity indexes and ratios between isodose volumes. Furthermore, a recently proposed index for comparison of radiosurgery plans was calculated. The new index balances conformity and steepness of the gradient outside the PTV. Results: Homogeneity index ranged from 1.35 to 2.00 (mean 1.54) for the Cyberknife and from 1.10 to 1.64 (mean 1.26) for IMRT. Conformity index ranged from 0.76 to 1.28 for the Cyberknife and from 0.79 to 2.55 for IMRT; the mean deviation of the conformity index from 1 was 0.14 and 0.74, respectively. The ratio between 20% and 80% isodose volumes ranged from 4.0 to 28.0 (mean 12.9) for the Cyberknife and from 9.7 to 38.3 (mean 21.7) for IMRT. Results obtained with the new index confirmed the behavior observed with the conformity index. Conclusion: Conformity resulted in general better for the Cyberknife while homogeneity resulted in general better for IMRT. The ratio between volumes of mid‐low isodose surfaces (10% – 50%) to the volume of the reference isodose surface (80%) resulted higher for IMRT than for the Cyberknife.

Purpose: to prove the feasibility of non‐rigid registration of CT scans taken from a temporal series in thoracic and abdominal radiosurgery.Method and Materials: for 5 patients 2 CT scans were acquired in end‐exhale and end‐inhale condition. The radiation oncologist identified the lesion in both examinations. We chose a voxel‐based non‐rigid registration using B‐Splines Free Form Deformation (FFD) with a local rigidity constraint. We created a mask to include only the target and applied the calculated deformation to it to evaluate position and shape of the lesion. We estimated the mass centres of target displacement between two moments of the breathing cycle and evaluated the variation of the volumes. Results: from the analysis of the mass centre movements it follows that the maximum displacement was in inferior/superior direction. The most relevant case was a lesion placed close to the diaphragm that showed large movements in anterior/posterior direction and also in the inferior/superior direction (18.6 mm). Volume variations were equal to 15% in two cases, 1.5% and 6 % in other two. Only a small lung lesion showed a big increase, due to the fact that this target contained a margin of nearby tissue affected by large deformation during the breathing cycle. The targets obtained by non‐rigid registration were similar to those identified by the radiation oncologist.Conclusion: this study shows the possibility to apply non‐rigid registration for a more accurate radiosurgerytreatment. In particular, among the applications of this study it should be possible to follow the target movements/deformations and calculate the dose distribution by taking into account the changes of tissues during all the instants of breathing, providing both the complete target tracking and the dynamic treatment planning.

Purpose: To propose dosimetric guidelines specifically designed for the Cyberknife radiosurgery system. Non‐availability of 10×10cm2 field and use of small circular collimators (5mm to 60mm) pose serious problems, that have been faced in this study by means of 8 different detectors and Monte Carlo simulation. This work is oriented to measurement of total scatter factors (Sc,p) and to reference dosimetry, though indications will also be given in view of a comprehensive guideline. Method and Materials: PTW PinPoint 31014, Exradin A16 and T14P microchambers, TN 502RDM micromosfet, PTW 30008 diode and TM60003 diamond, MD55 and EBT radiochromic films were used to measure Sc,p. Monte Carlo simulations (BEAMnrc) were used to produce phase space descriptions at the exit plane of each collimator, to calculate: 1) theoretical Sc,p values in water, and 2) correction factors to be applied to Sc,p as measured by 5 detectors (PinPoint, A16, T14P, diode, diamond), obtained by simulating shape and chemical composition of each detector. BEAMnrc was also used to calculate stopping power ratios and chamber correction factors for the Cyberknife linac, to decide whether values of kQ from the IAEA398 protocol could be applied without using a 10×10cm2 field. Results: Sc,p of the 5mm collimator as measured by simulated detectors averaged 0.653 − 9%+14%. Variation for larger collimators was smaller. After Monte Carlo correction, Sc,p of the 5mm collimator became 0.686 −2%+1%. Pure Monte Carlo calculation gave Sc,p=0.715 +/−1%. Calculation of correction factors showed that kQ values for the investigated chambers could be chosen when using IAEA398, introducing +/−0.2% uncertainty. Conclusion: Pure Monte Carlo calculation gave higher values of Sc,p compared to Monte Carlo‐corrected measurement. The latter is to be preferred because correction factors are less sensitive to beam parameters than pure calculation of Sc,p. For determination of Sc,p use of microchambers and Monte Carlo correction is recommended.

Purpose: functional magnetic resonance (fMRI) identifies areas related to different modality tasks. It is possible to identify particular areas in the brain which can be considered like “functional organs at risk” (fOARs). The aim of this study is to describe a method to exploit this functional information for the identification of fOAR in radiosurgery treatment planning. Method and Materials: for a patient who underwent radiosurgery treatment, CT and 60 EPI MR volumes were acquired for BOLD analysis of functional areas. Tasks were chosen on the base of the lesion location. The functional maps obtained by Statistical Parametric Mapping (SPM) software refer to the template volume: if one wants to exploit this information for patient treatment, it is necessary to calculate the deformation field which maps the template onto the CT. Treatment planning was performed using the CyberKnife radisourgery system. Results: the method has been applied to a patient with a right frontal metastasis of breast cancer. We have performed BOLD analysis of the motor function with self-passed left hand and left foot tasks, and of language related areas using category generation task (CGT), letter generation task (LGT), and simple questions task (SQT). It has been found that the activation of the 2 motor tasks was very close to the lesion while for the CGT, LGT and SQT studies the most significant constraint deals with the language associative areas located in the dorso-lateral frontal cortex (Brodman areas 8 –9). Conclusion: treatment plans studied with and without considering the fOARs were significantly different, in particular for the Dose Volume Histograms (DVH), while maintaining dose indices almost constant (homogeneity equal to 1.15 with fOARs and 1.18 without fOARs; conformity equal to 1 for both plans), proving a potential role of fMRI in radiosurgery.

Purpose: To compare experimental results from different detectors to Monte Carlo simulation in the dosimetry of small fields employed in the Cyberknife radiosurgery system. The Monte Carlo code has also been used to decide whether protocols that require a 10×10 cm2 field can be used for dosimetry under reference conditions. Method and Materials: Total scatter factors (sc,p) have been measured by means of the PTW PinPoint, Exradin A16 and T14P microchambers, Thomson and Nielsen micromosfet, PTW diamond and diode detectors, and MD 55-2 radiochromic films. A Monte Carlo calculation (BEAM code) was used to simulate the Cyberknife linac and to calculate sc,p and correction factors to be applied to raw data for various detectors. Two Farmer-type chambers were also simulated in order to calculate the ratio between kQ factors for the Cyberknife and of for a standard 6MV linac. Results: Monte Carlo simulations gave results in agreement within ±1% with experimental results for sc,p, PDD and profiles for collimators above 10 mm. Results for sc,p of smaller collimators (5 to 10 mm) agreed with radiochromic film measurements within ± 2%, while results with ionization chambers and diamond suffer from a systematic underestimation, resolved after application of the Monte Carlo correction factor. Micro-mosfet detectors showed good results as compared to Monte Carlo and radiochromic films, but suffered from poor reproducibility. The PTW diode detector seemed to systematically overestimate sc,p values; for the 5 mm collimator, a value of 0.746 has been obtained versus values in the range 0.67–0.71 obtained with Monte Carlo, radiochromic films, ionization chambers and diamond. The ratio between kQ factors at different beam qualities is 1.002 ± 0.5%. Conclusion: Monte Carlo can be used in the dosimetry of small beams to help solve experimental problems due to the finite dimension and to non-water equivalence of the detectors.