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Introduction: A multicenter phase II study for assessing the efficacy and the toxicity of hypofractionated radiotherapy with SIB plus temozolomide in patients with glioblastoma was carried out by the Brain Study Group of the Italian Association of Radiation Oncology., Methods: Twenty-four patients with newly diagnosed glioblastoma belonging to Recursive Partitioning Analysis classes III and IV were enrolled. The prescribed dose was 52.5 Gy in 15 fractions of 3.5 Gy and 67.5 in 15 fractions of 4.5 Gy to the SIB volume. Dose constraints for the hypofractionated schedule were provided. Radiotherapy was associated with concomitant and sequential temozolomide., Results: Median overall survival (OS) was 15.1 months, while median progression-free survival (PFS) was 8.6 months. Actuarial OS at 12 months was 65.6% ± 0.09, whereas actuarial PFS at 12 months was 41.2% ± 0.10. Status of methylation of MGMT promoter resulted to be a significant prognostic factor for OS. Radiotherapy-related acute toxicity was not relevant. Three patients (12.5%) had G3 myelotoxicity that required temozolomide temporary interruption or dose reduction during the chemotherapy. However, chemotherapy was not definitely discontinued for toxicity in any case. One patient out of 24 (4.2%) developed radionecrosis that required surgical resection with no evidence of disease in the surgical specimen., Conclusions: This trial confirms that hypofractionated radiotherapy with SIB and association with temozolomide may be a reasonable and feasible option for good prognosis patients with GBM.

Purpose: We present the γTools, a new phantom designed to assess geometric and dosimetric accuracy in Gamma Knife treatments, together with first tests and results of applications., Methods: The phantom is composed of two modules: the imaging module, a regular grid of 1660 control points to evaluate image distortions and image registration result and the dosimetry module for delivered dose distribution measurements. The phantom is accompanied by a MatLab routine for image distortions quantification. Dose measurement are performed with Gafchromic films fixed between two inserts and placed in various positions and orientations inside the dosimetry module thus covering a volume comparable to the full volume of a head., Results: Tests performed to assess the accuracy and precision of the imaging module demonstrated sub-millimetric values. As an example of possible applications, the phantom was employed to measure image distortions of two MRI scanners and to perform dosimetric studies of single shots delivered to homogeneous and heterogeneous materials. Due to the phantom material, the measured absolute dose do not correspond to the planned dose; doses comparisons are thus carried out between normalized dose distributions. Finally, an end-to-end test was carried out in the treatment of a neuroma-like target which resulted in a 100% gamma passing rate (2% local, 2 mm) and a distance between the real target perimeter and the prescription isodose centroids of about 1 mm., Conclusions: The tests demonstrate that the proposed phantom is suitable to assess both the geometrical and relative dosimetric accuracy of Gamma Knife radiosurgery treatments., (Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

The purpose of this study was to characterize a new single large-area ionization chamber, the integral quality monitor system (iRT, Germany), for online and real-time beam monitoring. Signal stability, monitor unit (MU) linearity and dose rate dependence were investigated for static and arc deliveries and compared to independent ionization chamber measurements. The dose verification capability of the transmission detector system was evaluated by comparing calculated and measured detector signals for 15 volumetric modulated arc therapy plans. The error detection sensitivity was tested by introducing MLC position and linac output errors. Deviations in dose distributions between the original and error-induced plans were compared in terms of detector signal deviation, dose-volume histogram (DVH) metrics and 2D γ-evaluation (2%/2 mm and 3%/3 mm). The detector signal is linearly dependent on linac output and shows negligible (<0.4%) dose rate dependence up to 460 MU min -1 . Signal stability is within 1% for cumulative detector output; substantial variations were observed for the segment-by-segment signal. Calculated versus measured cumulative signal deviations ranged from  -0.16%-2.25%. DVH, mean 2D γ-value and detector signal evaluations showed increasing deviations with regard to the respective reference with growing MLC and dose output errors; good correlation between DVH metrics and detector signal deviation was found (e.g. PTV D mean : R 2   =  0.97). Positional MLC errors of 1 mm and errors in linac output of 2% were identified with the transmission detector system. The extensive tests performed in this investigation show that the new transmission detector provides a stable and sensitive cumulative signal output and is suitable for beam monitoring during patient treatment.

Purpose: Radiosurgery (RS) is a well-established treatment in selected patients with brain metastasis. The aim of this study is to compare the differences between CyberKnife (CK) and TomoTherapy (HT) treatment plans of RS of single brain metastasis (BM) to define when HT should be used in cases beyond Cyberknife-when both systems are readily available for the radiation oncologist., Methods and Materials: Nineteen patients with single brain metastasis treated with CK were re-planned for radiosurgery using TomoTherapy Hi-ART system. Two planning approaches have been used for TomoTherapy plans: the classical one (HT) and the improved conformity (icHT) that produces dose distributions more similar to those of RS plans. PTV coverage, Conformity Index (CI), Paddick Conformity Index (nCI), Homogeneity Index (HI), Gradient Index (GI), and beam on time of CK, HT, and icHT plans were evaluated and compared., Results: A good coverage was found for CK, HT, and icHT plans. A difference between mean HI of CK and icHT plans was observed (p = 0.007). Better dose gradients compared to both icHT and HT modalities were observed in CK plans. icHT modality showed improved mean CI respect to HT modality, similar to that obtained in CK plans., Conclusions: CK plans show higher conformity and lower GI than icHT and HT plans. TomoTherapy demonstrates the advantage of being a device capable to reach different clinical objectives depending on the different planning modality employed. CyberKnife and TomoTherapy are both optimal RS devices, the choice to use one over another has to be clinically guided.

Background: Accelerated partial breast irradiation (APBI) represents a valid option for selected early breast cancer (BC). We recently published the 5-year results of the APBI-IMRT-Florence phase 3 randomised trial (NCT02104895), showing a very low rate of disease failure, with acute and early-late toxicity in favour of APBI. We present the early and 2-year follow-up health-related quality of life (HRQoL) results., Methods: Eligible patients were women aged more than 40 years with early BC suitable for breast-conserving surgery. APBI consisted of 30 Gy in five fractions delivered with IMRT technique. Standard whole breast irradiation (WBI) consisted of 50 Gy in 25 fractions plus a 10 Gy in five fractions boost on tumour bed. A total of 520 patients were enrolled in the phase 3 trial. Overall, 205 patients (105 APBI and 100 WBI) fully completed all the given questionnaires and were therefore included in the present analysis. As HRQoL assessment, patients were asked to complete the European Organisation for Research and Treatment of Cancer QLQ-C30, and the BR23 questionnaires at the beginning (T0), at the end (T1) and after 2 years from radiation (T2)., Findings: No significant difference between the two arms at QLQ-C30 and BR23 scores emerged at T0. Global health status (p = 0.0001), and most scores of the functional and symptom scales of QLQ-C30 at T1 showed significant differences in favour of the APBI arm. Concerning the BR23 functional and symptom scales, the body image perception, future perspective and breast and arm symptoms were significantly better in the APBI group. Similar significant results emerged at T2: significant differences in favour of APBI emerged for GHS (p = 0.0001), and most functional and symptom QLQ-C30 scales. According to QLQ-BR23 module, among the functional scales, the body image perception and the future perspective were significantly better in the APBI group (p = 0.0001), whereas among the symptom scales significant difference emerged by breast and arm symptoms with better outcomes in APBI arm (p < 0.01)., Interpretation: Early BC treated with APBI showed an improved short-term, and 2-year follow-up HRQoL outcome as compared with WBI. Early BC treated with APBI showed an improved short-term, and 2-year follow-up HRQoL outcome as compared with WBI. APBI should be strongly considered in the treatment choice for selected low-risk patients. Mature local control results from ongoing adequately powered randomised trials are awaited., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The application of high precision hypofractionated regimes (a.k.a. stereotactic body radiotherapy (SBRT)) to the treatment of lung cancer is a 'success story' of radiotherapy. From the technical perspective, lung SBRT is a challenging technique as all aspects of the treatment workflow, from imaging to dose calculation to treatment delivery, should be carefully handled in order to ensure consistency between planned and delivered dose. In this review such technical aspects are presented and discussed, looking at what has been developed over the years. The use of imaging techniques such as slow-CT, breath-hold CT, four-dimensional CT and mid-ventilation is reviewed, presenting the main characteristics of each approach but not necessarily to single out 'the best' solution. Concerning dose calculation, a number of studies clearly separate dose algorithms that should be considered inadequate for lung SBRT (e.g. simple pencil beam algorithms) from approaches such as convolution algorithms, Monte Carlo, and solution of the transport equation, that are much better at handling the combination of small fields and heterogenenous geometries that make dose calculation not trivial. Patient positioning and management of intrafraction motion have been two areas of significant developments, to the point where it is difficult to identify which solution represents the best compromise between technical complexity and clinical effectiveness. The review analyses several of these methods, outlining the residual uncertainties associated with each of them. Last but not least, two subjects are discussed, adaptive therapy and particle therapy, that may represent in the near future additional tools for the technical improvement of lung SBRT., (Copyright © 2017. Published by Elsevier Ltd.)

Purpose: To evaluate EBT3 for pre-treatment patient specific quality assurance (QA). The method we propose combines the experience gained in our center with the guidelines of the protocol proposed by Lewis et al. in 2012. To compare the multichannel approach with the single channel dosimetry., Methods: Gafchromic® EBT3 films were irradiated both at linac and TomoTherapy and calibration curves were obtained. A series of irradiations with simple fields (uniform dose distributions on regular shaped targets) was performed. In a second stage, films were exposed to full clinical plans at linac (step and shoot IMRT and VMAT). At TomoTherapy dose maps were obtained for a clinical plan in three different coronal planes. Films were digitized using an Epson 10000XL scanner and FilmQA™ Pro software was employed for the analysis., Results: The measured calibration curves suggest that, at least for the two beams taken into account (6 MV linac and TomoTherapy), a single calibration can be successfully adopted for each film lot. The application of the multichannel optimization method strongly improves the results in terms of gamma passing rates of the comparison between measured and calculated maps., Conclusions: Up to now EBT films, although attractive, were not preferred for routine patient specific QA due to their complex and time consuming processing and to the challenging work of characterization. The application of the mentioned protocol, together with some additional precautions, and the adoption of the multichannel optimization dosimetry, make this detector a handy and reliable tool for patient specific QA., (Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.)

Purpose: The aim of our study was to evaluate the usefulness of the four-dimensional computed tomography (4DCT) in accelerated partial breast irradiation (aPBI) planning., Materials and Methods: At our Institute, we have been treating the index quadrant with external intensity-modulated radiation therapy in a phase III trial. For this study, we selected a sample of 10 patients with right- or left-sided breast cancer and surgical clips at the excision site. Contouring of the target was performed both using three-dimensional computed tomography (3DCT) and 4DCT imaging. On both 3DCT and 4DCT, we recorded the clinical target volume (CTV) and the planning target volume (PTV) and the coordinates of the PTV centroid. We calculated the treatment plans, according to our protocol, using the contours drawn on the 3DCT and 4DCT and evaluated target coverage and sparing of organs at risk (OAR)., Results: Median age of the patients was 63.5 years (range 52-75). The comparison between the 3DCT and 4DCT PTV volumes was not statistically significant (p = 0.79). Concerning centroid coordinates, the average absolute differences were 0.1 mm in the latero-lateral, 0.7 mm in the antero-posterior and 0.3 mm in the supero-inferior direction. No statistically significant differences were observed both in PTV coverage and OAR sparing; the 4D PTV contour is adequately covered when the plan based on the 3D contours is used. Target coverage was reduced on average by 1 % and no statistically significant difference was observed (p = 0.93)., Conclusions: In our experience, no significant differences between PTV volumes, PTV coverage, OAR sparing and centroid position are evidenced when comparing 3DCT and 4DCT plans. Conventional 3DCT-based planning is adequate for aPBI.

The purpose of this study was to report the efficacy and the safety profile on the subset of selected early breast cancer (BC) patients aged 70 years or older from a single-center phase 3 trial comparing whole breast irradiation (WBI) to accelerated partial breast irradiation (APBI) using intensity-modulated radiation therapy technique. Between 2005 and 2013, 520 patients aged more than 40 years old were enrolled and randomly assigned to receive either WBI or APBI in a 1:1 ratio. Eligible patients were women with early BC (maximum diameter 2.5 cm) suitable for breast conserving surgery. This study is registered with ClinicalTrials.gov, NCT02104895. A total of 117 patients aged 70 years or more were analyzed (58 in the WBI arm, 59 in the APBI arm). At a median follow-up of 5-years (range 3.4-7.0), the ipsilateral breast tumor recurrence (IBTR) rate was 1.9 % in both groups. No significant difference between the two groups was identified (log-rank test p = 0.96). The 5-year disease-free survival (DFS) rates in the WBI group and APBI group were 6.1 and 1.9 %, respectively (p = 0.33). The APBI group presented significantly better results in terms of acute skin toxicity, considering both any grade (p = 0.0001) and grade 2 or higher (p = 0.0001). Our subgroup analyses showed a very low rate and no significant difference in terms of IBTR, using both WBI and APBI. A significant impact on patients compliance in terms of acute and early late toxicity was shown, which could translate in a consistent improvement of overall quality of life.

Aim: The aim of this study was to compare surface imaging, portal imaging, and skin marker set-up in radiotherapy of thoracic and pelvic regions, using cone beam computed tomography (CBCT) data as the gold standard., Patients and Methods: Twenty patients were included in this study. CBCT, surface acquisition (SA), and two orthogonal portal images (PI) were acquired during the first four treatment sessions. Patient set-up corrections, obtained by registering the planning CT with CBCT, were used as the gold standard. Registration results of the PI and SA were evaluated and compared with those obtained with CBCT. The advantage derived from using SA or PI verification systems over a skin marker set-up was also quantified., Results: A statistically significant difference between PI and SA (in favour of PI) was observed in seven patients undergoing treatment of the pelvic region and in two patients undergoing treatment of the thoracic region. The use of SA or PI, compared with a skin marker set-up, improved patient positioning in 50% and 57% of the thoracic fractions, respectively. For pelvic fractions, the use of PI was beneficial in 73% of the cases, while the use of SA was beneficial in only 45%. Patient positioning worsened with SA, particularly along longitudinal and vertical directions., Conclusion: PI yielded more accurate registration results than SA for both pelvic and thoracic fractions. Compared with the skin marker set-up, PI performances were superior to SA for pelvic fractions while comparable results were obtained for thoracic fractions.

Background: Accelerated partial breast irradiation (APBI) has been introduced as an alternative treatment method for selected patients with early stage breast cancer (BC). Intensity-modulated radiotherapy (IMRT) has the theoretical advantage of a further increase in dose conformity compared with three-dimensional techniques, with more normal tissue sparing. The aim of this randomised trial is to compare the local recurrence and survival of APBI using the IMRT technique after breast-conserving surgery to conventional whole-breast irradiation (WBI) in early stage BC., Methods: This study was performed at the University of Florence (Florence, Italy). Women aged more than 40years affected by early BC, with a maximum pathological tumour size of 25mm, were randomly assigned in a 1:1 ratio to receive either WBI or APBI using IMRT. Patients in the APBI arm received a total dose of 30 Gy to the tumour bed in five daily fractions. The WBI arm received 50Gy in 25 fractions, followed by a boost on the tumour bed of 10Gy in five fractions. The primary end-point was occurrence of ipsilateral breast tumour recurrences (IBTRs); the main analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT02104895., Findings: A total of 520 patients were randomised (260 to external WBI and 260 to APBI with IMRT) between March 2005 and June 2013. At a median follow-up of 5.0 years (Interquartile Range (IQR) 3.4-7.0), the IBTR rate was 1.5% (three cases) in the APBI group (95% confidence interval (CI) 0.1-3.0) and in the WBI group (three cases; 95% CI 0.0-2.8). No significant difference emerged between the two groups (log rank test p=0.86). We identified seven deaths in the WBI group and only one in the APBI group (p=0.057). The 5-year overall survival was 96.6% for the WBI group and 99.4% for the APBI group. The APBI group presented significantly better results considering acute (p=0.0001), late (p=0.004), and cosmetic outcome (p=0.045)., Interpretation: To our knowledge, this is the first randomised study using the IMRT technique for APBI delivery. No significant difference in terms of IBTR and overall survival was observed between the two arms. APBI displayed a significantly better toxicity profile., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Linac-based stereotactic radiosurgery (SRS) has been widely used for treating small intracranial lesions. This technique allows conforming the dose distribution to the planning target volume (PTV), providing a steep dose gradient with the surrounding normal tissues. This is realized through dedicated collimation systems. The present study aims to compare SRS plans with two collimating systems: the beam modulator (BM) of the Elekta Synergy linac and the DirexGroup micromultileaf collimator (μMLC). Seventeen patients (25 PTVs) were planned both with BM and μMLC (mounted on an Elekta Precise linac) using the Odyssey (PerMedics) treatment planning system (TPS). Plans were compared in terms of dose-volume histograms (DVH), minimum dose to the PTV, conformity index (CI), and homogeneity index (HI), as defined by the TPS, and doses to relevant organs at risk (OAR). The mean difference between the μMLC and the BM plans in minimum PTV dose was 5.7% ± 4.2% in favor of the μMLC plans. No statistically significant difference was found between the distributions of the CI values for the two planning modalities (p = 0.54), while the difference between the distributions of the HI values was statistically significant (p = 0.018). For both BM and μMLC plans, no differences were observed in CI and HI, depending on lesion size and shape. The PTV homogeneity achieved by BM plans was 15.1% ± 6.8% compared to 10.4% ± 6.6% with μMLC. Higher maximum and mean doses to OAR were observed in the BM plans; however, for both plans, dose constraints were respected. The comparison between the two collimating systems showed no substantial differences in terms of PTV coverage or OAR sparing. The improvements obtained by using μMLC are relatively small, and both systems turned out to be adequate for SRS treatments.

Purpose: In lung cancer, a high radiation dose to the target area correlates with better local control but is frequently counterbalanced by a higher risk of lung toxicity. Several methods exist to coordinate respiratory motion in lung radiotherapy. We aimed to investigate the impact of a breathing-control system on irradiated volumes and dosimetric parameters in three-dimensional conformal radiotherapy (3D-CRT) and stereotactic radiotherapy (SRT) treatments., Materials and Methods: Twelve patients were scheduled for radical radiotherapy: five for SRT and seven for 3D-CRT. For each patient, in addition to the free-breathing computed tomography (CT) scan, four additional sets of CT slices were acquired using the Active Breathing Coordinator device (ABC, Elekta Oncology Systems Ltd., UK)., Results: The volumes acquired with the ABC device were significantly smaller than the free-breathing volumes [23 % reduction of planning tumour volume (PTV), p = 0.002]. ABC allowed a reduction of all dosimetric parameters [2.28 % reduction of percentage volume of lung treated to a dose of ≥ 20 Gy (V20), p = 0.004; 10 % reduction of mean lung dose (MLD), p = 0.009]. Significant differences were found both in SRT and in 3D-CRT, in peripheral and apical lesions., Conclusion: In our experience, ABC has the potential to reduce lung toxicity in the treatment of lung cancer; alternatively, it can allow the prescribed dose to be increased while maintaining the same risk of lung toxicity.

Objectives/hypothesis: To review toxicity and outcomes in patients with head and neck cancer treated with simultaneous integrated boost-intensity-modulated radiotherapy (SIB-IMRT)., Study Design: Review of experience with the SIB-IMRT technique., Methods: Fifty patients were treated with the SIB-IMRT technique. Two possible schedules of radiation therapy (RT) were used: SIB 70 (70/60/54 in 33 fractions) and SIB 66 (66/60/54 in 33 fractions). Forty-one patients also received chemotherapy., Results: All but two patients completed treatment as prescribed. No G4 acute toxicity has been reported in our series. We did not observe any G3 to G4 chronic toxicity, apart from one case of cutaneous necrosis. After a median follow-up of 23.3 months (range, 1-60 months), 41 patients (82%) were alive and negative for disease, and one patient (2%) was alive with distant metastases. Eight patients (16%) died, seven because of progressive disease and one for other causes., Conclusions: SIB-IMRT is a highly effective and safe technique of RT in the treatment of head and neck cancer., (Copyright © 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

Purpose: This study sought to evaluate acute toxicity and local control in patients who underwent extracranial stereotactic body radiation therapy (SBRT) for paracardiac and cardiac metastatic lesions, defined as such when located at a maximum distance of 1 cm from the heart or inside its parenchyma., Materials and Methods: Between January 2009 and May 2011, 16 patients with paracardiac and cardiac lesions were treated with SBRT. For dose specification, in 15 of 16 patients, the prescription dosage was 36 Gy in three fractions (70% isodose). In one patient, the target lesion was inside the heart, and the prescription dosage was 30 Gy in three fractions (70% isodose)., Results: Regarding response to stereotactic radiotherapy, we recorded one (6%) complete response (CR), six (37%) partial responses (PR), five (32%) stable disease (SD) and four (25%) local failures. Median interval to local failure was 5.2 (range, 3-12) months. The cause of death was distant progression of disease in all four patients. Compliance to treatment was excellent; no patient developed cardiological symptoms or electrocardiographic abnormalities, even months after SBRT., Conclusions: Results of our retrospective study indicate that SBRT represents a safe and effective treatment option for patients with cardiac and paracardiac metastases.

Purpose: To investigate the outcome of invasive early breast cancer patients that underwent breast-conserving surgery and adjuvant radiotherapy (RT), treated with a prospective margin-directed institutional policy for RT boost dose, based on final margins status (FMS)., Methods and Materials: A total of 2093 patients were treated between 2000 and 2008. 10 Gy boost was prescribed in case of FMS>5mm; 16 Gy boost with FMS between 2 and 5mm; 20 Gy boost in case of FMS<2mm or positive., Results: After a median follow up of 5.2 years, we recorded 41 local relapse (LR, 2%). Concerning LR free survival, age at diagnosis, nuclear grade, hormonal status, T-stage, adjuvant hormonal therapy and adjuvant chemotherapy emerged as significant parameters (p-values from log rank test <0.05). FMS, that directed the RT boost dose, did not have significant impact on LRFS (p=0.46). LR rates were 2.3% for FMS<2mm, 2.6% for 2-5mm FMS and 1.8% for FMS>5mm. At multivariate analysis, higher nuclear grade (p=0.045), triple negative subtype (p=0.036) and higher T-stage (p=0.02) resulted as the independent predictors of LR occurrence., Conclusions: Our experience showed that a margin-directed policy of RT boost dose-escalation seems to reduce the negative impact of FMS on LR, but it is not able to overcome the unfavorable effect of higher nuclear grade, higher T stage and triple negative subtype., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The aim of this paper is to investigate the accuracy of a laser∕camera surface imaging system (Sentinel) when used on patients treated in the thorax or pelvic regions and to evaluate system employment conditions and patient setup procedures that provide more accurate results., Methods: The system was tested on two groups of patients for whom different patient setup procedures and Sentinel employment conditions were considered. For the first group of 33 patients (FG) no changes to the usual setup procedures were made and a surface extension limited to the treated region was considered. For the second group of 14 patients (SG) the reproducibility of external body surfaces, including body parts not in close proximity to the treatment site, was optimized and a wider surface was captured. In all cases the system accuracy was evaluated comparing registration results from concurrent Sentinel and cone beam CT (CBCT) acquisitions for a total of 192 occasions. External body surfaces, extracted from planning CT studies, were used as reference in both cases, but for SG also surface data captured by Sentinel system at the first treatment were employed., Results: In the 90th percentile of the distributions reporting CBCT and Sentinel registration parameters, absolute differences for FG were less than 6.4 mm and 3.8°. Better performances were observed for SG (≤5.7 mm and 2°). Mean absolute differences between three translation and three rotation parameters of CBCT and Sentinel were: less than 3.5 mm and 2.1° and 3.7 mm and 1.3° in FG for thorax and pelvis, respectively, and less than 2.8 mm and 1° and 2.7 mm and 0.9° for pelvis and thorax, respectively, in SG. No advantage in considering surface data captured by Sentinel as a reference instead of the surface extracted from the planning CT was observed., Conclusions: The accuracy of Sentinel system in detecting errors is influenced by the extension and reliability of the surface used. When the reproducibility of external body surfaces was optimized differences between CBCT and Sentinel registration parameters resulted less than 5.7 mm and 2° in the 90% of the pelvis and thorax considered cases. No advantage in considering a Sentinel acquisition as reference was observed.

Aims and Background: Waiting time for radiotherapy is a major problem in clinical practice. We developed a model to create a priority list of patients waiting for radiotherapy according to clinical criteria, where booking of patients is not on a "first-come, first-served" basis and where prioritization has not been left up to individual discretion., Methods: The system is based on an algorithm that assigns to each patient a personal code (priority code, PC) that can be used as a continuous variable to have a priority list. PCpatient = D0patient + PWTsubgroup of treatment. Palliative treatments were categorized according to the clinical urgency. Radical treatments were stratified by primary tumors, by the setting of treatment (preoperative, curative, postoperative) and by the main prognostic factors. Each subgroup of patients has a "priority waiting time" (PWT subgroup of treatment). Calculation of the PC starts from a differentiated date according to clinical scenario [Reference date (D0)], which is taken from the clinical history of the patient., Results: Patients are differentiated according to clinical criteria and according to time elapsed from diagnosis. The priority list can be automatically updated day by day. Delays in patient referral or imaging availability are minimized., Conclusions: The model represents a tool for an objective and automatic prioritization of the patients who are waiting for radiotherapy.

Background: Meningeal carcinomatosis (MC) is a rare complication in breast cancer (BC) with no efficient modality of treatment yet found; overall survival (OS) generally did not exceed six months. We reviewed the experience of the University of Florence focusing on prognostic factors and MC survival., Patients and Methods: We analyzed 33 patients treated for MC from BC between 2002 and 2010., Results: Mean OS from MC diagnosis was 4.9 months. At survival analysis clinical stage emerged as the only statistical significant parameter (P = 0.009) among BC diagnosis features. Among MC diagnosis parameters, more than three metastases at diagnosis (P = 0.037), multimodality treatment (P = 0.014) and poor performance status (P = 0.003) reached the statistical significance. At multivariate analysis only performance status at MC diagnosis maintained the statistical significance (P = 0.0047; HR: 3.34; CI 95% 1.45-7.73)., Conclusions: Our experience confirms that performance status is probably the most important prognostic factor in these patients. Multimodality approach is probably the best option.

Purpose: The aim of this study is to investigate the performance of Sentinel(™), a patient setup verification device based on a laser/camera system, when used on rigid-body phantoms., Methods: The Sentinel system consists of a scanner unit, containing the laser and the camera, and surface-matching registration software. For the registration procedure, both a computed tomography (CT) and a Sentinel image can be used as a reference. Tests were performed on phantoms using an Elekta Synergy(®) beam modulator Linac equipped with a cone beam CT (CBCT), a HexaPOD RT couch top, and an iViewGT portal imaging system. Experiments conducted in this study tested reproducibility of the Sentinel surface acquisition and of set-up procedure, accuracy in quantifying known phantom mispositioning, and compared Sentinel, CBCT, and portal imaging system performance., Results: Reproducibility of surface acquisition and setup procedure was better than 0.5 mm and 0.5° and 1 mm and 0.4°, respectively. The system accuracy was better than 1 mm and 1° when a Sentinel image was used as reference. A global worsening of Sentinel performance was observed using as reference an external surface extracted from CT study. This effect is probably due to small differences in considered surfaces, caused by different imaging modalities. The results obtained by testing the system on rigid phantoms were comparable to those obtained using CBCT and better than those obtained with conventional portal imaging systems., Conclusions: The Sentinel setup verification device is a reproducible and consistent system able to detect misalignments with accuracy better than 1 mm and 1°. When tested on rigid body phantoms, Sentinel and CBCT performed similarly. When compared to portal imaging, both Sentinel and CBCT were more accurate.

Background and Purpose: To evaluate survival, locoregional control and toxicity in a series of 56 mesothelioma patients treated from May 2005 to May 2010 with post-operative radiotherapy after extrapleural pneumonectomy (EPP) in three Italian Institutions (Brescia, Florence, and Modena)., Material and Methods: Fifty-six patients treated with adjuvant radiotherapy (RT) after EPP were analyzed. Four patients were treated with 3DCRT, 50 with IMRT and two with helical tomotherapy. Forty-five to 50 Gy in 25 fractions were given to the affected hemithorax and to ipsilateral mediastinum, with a simultaneous integrated boost to the sites of microscopically involved margins up to 60 Gy in 20/56 cases., Results: Three year locoregional control (LRC), distant metastasis free (DMF), disease free (DF), disease specific (DSS) and overall survival (OS) rates are 90%, 66%, 57%, 62%, and 60%, respectively., Conclusion: Postoperative RT with modern techniques is an effective method to obtain excellent local control and cure rates in mesothelioma patients submitted to EPP., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: This study was done to evaluate the toxicity related to concurrent radiotherapy and anthracycline (AC)-based chemotherapy in the adjuvant treatment of early breast cancer and to investigate the impact of treatment interruptions and the feasibility of this uncommon therapeutic approach., Materials and Methods: From September 2002 to December 2007, 60 patients were treated at our Centre. The mean age at presentation was 48.5 (range 38-64) years. All patients underwent conservative surgery, and radiotherapy to the entire breast (mean dose 50 Gy; range 46-52 Gy). AC-based regimens consisted of four cycles of AC (doxorubicin plus cyclophosphamide) or four cycles of epirubicin (EPI) followed by four courses of cyclophosphamide, methotrexate and 5-fluorouracil (CMF)., Results: Concomitant treatment caused acute skin G3 toxicity in 8.9% of patients and one case of G4 toxicity (1.7%). Concerning cardiac assessment, six of the 56 evaluable patients (10.7%) developed an asymptomatic decline of left ventricular ejection fraction >10% and <20% of the baseline value. Radiotherapy was temporarily stopped in 21.3% and chemotherapy in 57.1% of patients., Conclusions: In our experience, concomitant chemotherapy did not emerge as a significant factor in radiotherapy interruption. Moreover, no severe cardiac events were recorded.

Background and Purpose: Post-operative radiotherapy (PORT) in radically resected non-small cell lung cancer (NSCLC) has the aim to reduce loco regional recurrence and to improve overall survival. PORT has been evaluated in several trials but indication to post-operative treatment in N2 patients is still debated., Material and Methods: We retrospectively analyzed 175 patients treated at University of Florence between 1988 and 2004 with completely resected NSCLC stages IIIA-IIIB, N2 disease. Surgery consisted in a lobectomy in 58.9% and in a bi-lobectomy or in a pneumonectomy in 41.1% of patients. One hundred and nineteen patients underwent PORT and 56 patients did not receive PORT (no-PORT)., Results: At a median follow-up of 27.6 months (range 4-233 months), we found a significant reduction in local recurrence (LR) in PORT group (log-rank test p=0.015; HR: 0.45; 95%CI: 0.24-0.87). No statistical difference were found in terms of overall survival (OS) (log-rank test p=0.92). Concerning other prognostic factors, male sex emerged as statistically significant (HR:4.33;1.04-18.02) on local progression free survival (LPFS) at univariate analysis. Acute and long-term toxicity was mild., Conclusion: Our retrospective analysis showed that PORT may improve local disease control in N2 NSCLC patients with an acceptable treatment-related toxicity., (Published by Elsevier Ireland Ltd.)

Purpose: To evaluate with a randomized clinical trial the possibility of treating the index quadrant with external intensity-modulated radiotherapy (IMRT) in a selected group of patients with early-stage breast cancer and to analyze the acute toxicity., Methods and Materials: From September 2005, a randomized Phase III clinical trial has been conducted to compare conventional (tangential field) fractionated whole breast treatment (Arm A) with accelerated partial breast irradiation plus intensity-modulated radiotherapy (Arm B). For intensity-modulated radiotherapy, the clinical target volume was drawn with a uniform 1-cm margin around the surgical clips in three dimensions. The ipsilateral and contralateral breast, ipsilateral and contralateral lung, heart, and spinal cord were contoured as organs at risk. All the regions of interest were contoured according to the International Commission on Radiation Units and Measurements reports 50 and 62 recommendations., Results: In September 2008, 259 patients were randomized and treated. The mean clinical target volume in Arm B was 44 cm(3) and the mean planning target volume was 123 cm(3). The mean value of the ratio between the planning target volume and the ipsilateral breast volume was 21%. The rate of Grade 1 and Grade 2 acute skin toxicity was 22% and 19% in Arm A (Radiation Therapy Oncology Group scale), respectively. The tolerance in Arm B was excellent with only 5% Grade 1 and 0.8% Grade 2 acute skin toxicity. The planning constraints were fully satisfied in most patients. In a very few cases, this was not possible because of very unfavorable anatomy. Quality assurance procedures were performed according to our internal quality assurance protocol, with excellent results., Conclusion: In the present preliminary analysis, we have demonstrated that accelerated partial breast irradiation is feasible, with very low acute toxicity., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the outcome and predictive factors of patients who underwent breast-conserving surgery and adjuvant radiotherapy to the whole breast only, without supraclavicular nodal irradiation., Methods and Materials: A total of 5,717 patients with pT1-T4 breast cancer were treated at the University of Florence. The median age of the patient population was 55 years (range, 30-80 years). All patients were followed for a median of 6.8 years (range, 1-27 years). Adjuvant chemotherapy was recommended in 1,535 patients (26.9%). Tamoxifen was prescribed in 2,951 patients (51.6%). The patients were split into three groups according to number of positive axillary nodes (PAN): P1, negative axillary lymph nodes; P2, one to three PAN; P3, more than three PAN., Results: The P3 patients had a higher incidence of supraclavicular fossa recurrence (SFR) compared with P2 and P1 patients. However, the incidence of SFR in P3 patients was low (only 5.5%), whereas the incidence of distant metastases (DM) was 27.2%. Distant metastasis was the only independent prognostic factor for breast cancer survival. Additionally, in the subgroup of patients who developed local recurrence, DM was the most important death predictor., Conclusion: Our series suggests that isolated SFR in patients who did not receive supraclavicular radiotherapy is infrequent, as well as in those patients who have more than three PAN, and SFR seems not to influence the outcome, which depends on DM occurrence., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose: To analyze the relationship between a delay in radiotherapy (RT) after breast-conserving surgery and ipsilateral breast recurrence (BR)., Methods and Materials: We included in our analysis 4,820 breast cancer patients who had undergone postoperative RT at the University of Florence. The patients were categorized into four groups according to the interval between surgery and RT (T1, <60 days; T2, 61-120 days; T3, 121-180 days; and T4, >180 days)., Results: On multivariate analysis, the timing of RT did not reach statistical significance in patients who received only postoperative RT (n = 1,935) or RT and hormonal therapy (HT) (n = 1,684) or RT, chemotherapy (CHT), and HT (n = 529). In the postoperative RT-only group, age at presentation, surgical margin status, and a boost to the tumor bed were independent prognostic factors for BR. In the RT plus HT group, age at presentation and boost emerged as independent prognostic factors for BR (p = 0.006 and p = 0.049, respectively). Finally, in the RT, CHT, and HT group, only multifocality was an independent BR predictor (p = 0.01). Only in the group of patients treated with RT and CHT (n = 672) did multivariate analysis with stepwise selection show RT timing as an independent prognostic factor (hazard ratio, 1.59; 95% confidence interval, 1.01-2.52; p = 0.045). Analyzing this group of patients, we found that most patients included had worse prognostic factors and had received CHT consisting of cyclophosphamide, methotrexate, and 5-fluorouracil before undergoing RT., Conclusion: The results of our study have shown that the timing of RT itself does not affect local recurrence, which is mainly related to prognostic factors. Thus, the "waiting list" should be thought of as a "programming list," with patients scheduled for RT according to their prognostic factors.

The aim of this paper is to present a new phantom for arc therapy, intensity-modulated radiation therapy (IMRT), and tomotherapy dose distribution measurement in pretreatment verification. The presented phantom is innovative for its use of water as the tissue equivalent material, together with a technical solution specifically designed to support radiographic or radiochromic film and ionization chambers in any desired position. The phantom comprise a Plexiglas container, whose present shape and dimensions offer the possibility to simulate a human torso or abdomen; the container can be filled with water by opening the upper cover. On the internal side of the cover, a set of carbon pipes can support film in the desired coronal, axial, or sagittal planes. At one of the two ends of the phantom, an ionization chamber can be positioned parallel to the rotation axis of the accelerator gantry in all possible positions within a 20 cm diameter cylinder, for film calibration purposes. Inhomogeneities can be inserted into the phantom using the same carbon pipes and plastic sheets used to support film. An example of vertebra-shaped inserts made of bone equivalent material is reported. Radiochromic film can be dipped in water, while radiographic film must be protected to prevent damage. To accomplish this, radiographic film is laminated using a cold laminating film. In order to assess the effects of both the lamination itself and the effects of water on laminated Kodak EDR2 film, the optical density (OD) of conventional, laminated, and laminated film immersed in water and exposed to a range of doses from 0 to 300 cGy were compared. The OD of the three samples receiving the same radiation dose did not present any significant difference, thus proving that laminated EDR2 film can also be used in water. A prerequisite for any dosimetric comparison between planned and measured data is a proper film to plan registration. The solution proposed here is an extrinsic in-plane registration technique using four reference points marked on each film in predefined positions. The four points and the millimeter scales fixed on the carbon pipes that support the film are designed and manufactured so as to transfer onto the film the same reference system used during the planning procedure, thus allowing a straightforward registration. Tests to assess the accuracy of the proposed registration method demonstrate that the distances between measured and intended marker positions, evaluated for coronal, axial, and sagittal planes, were about 1 mm for both anteroposterior and lateral projections.