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The aim of this study was the production of the first Italian survey of radiation dose in computed tomography (CT) prior to the widespread adoption of multislice CT, in order to have a reference point to facilitate later investigation of dose exposure changes brought by this new CT modality. The collected dose data were compared with diagnostic reference levels (DRLs). The agreement between experimental dose evaluation and Monte Carlo (MC) simulations was investigated. The survey was carried out in 29 Italian hospitals, covered 48 CT scanners and 232 examinations. The dose-length product (DLP) and effective dose (E) values were estimated based on MC simulations for seven clinical protocols using the CT-Dose program. Statistical analysis showed a significant difference (p<0.01) in the DLP between the two methods, with MC values being greater than the experimental ones. For E, the MC values were greater in routine head (8.2%), cervical spine (2.7%) and lumbar spine (2.9%) studies. The weighted CT dose index, the DLP and E were always below the DRLs set by the European Community. This dose survey gives a good but incomplete picture of the Italian CT dose situation and may be useful as a reference baseline for defining clinical multislice protocols in the near future. [ABSTRACT FROM AUTHOR]

In this technical development report, we present the strategic placement of fiducial markers within the prostate under the guidance of computed tomography (CT) and electromagnetic navigation (EMN) for the delivery of ultra-hypofractionated cyberknife (CK) therapy in a patient with localized prostate cancer (PCa) who had previously undergone chemo-radiotherapy for rectal cancer and subsequent abdominoperineal resection due to local recurrence. The patient was positioned in a prone position with a pillow under the pelvis to facilitate access, and an electromagnetic fiducial marker was placed on the patient's skin to establish a stable position. CT scans were performed to plan the procedure, mark virtual points, and simulate the needle trajectory using the navigation system. Local anesthesia was administered, and a 21G needle was used to place the fiducial markers according to the navigation system information. A confirmatory CT scan was obtained to ensure proper positioning. The implantation procedure was safe, without any acute side effects such as pain, hematuria, dysuria, or hematospermia. Our report highlights the ability to use EMN systems to virtually navigate within a pre-acquired imaging dataset in the interventional room, allowing for non-conventional approaches and potentially revolutionizing fiducial marker positioning, offering new perspectives for PCa treatment in selected cases. [ABSTRACT FROM AUTHOR]

Simple Summary: The present study has been suggested by the previous experience of our group showing that patients treated with conventional radiotherapy (named 3D conformal radiotherapy—3D-CRT) performed after conservative surgery (CS) for tumors of the supraglottic regions experienced a high rate of severe long-term toxicity. Therefore, we reported the toxicity profile of a similar cohort of patients treated with a high-precision radiotherapy technique (named intensity-modulated radiotherapy—IMRT). Moreover, to investigate the advantage of IMRT, we performed a comparison with a historical cohort treated with 3D-CRT. Results showed that patients treated with IMRT achieved a very low toxicity profile and comparison with 3D-CRT was in favor of IMRTs. Therefore, we believe that the results of the present study provide preliminary findings on the potential of IMRT in improving the toxicity profile of patients treated with surgical organ preservation strategies for laryngeal tumors. The aim of the present study was to investigate the role of intensity-modulated radiotherapy (IMRT) on the toxicity profile of patients treated with conservative surgery (CS) of the supraglottic (SG) region. Data on patients treated with CS and postoperative radiotherapy (PORT)-IMRT were prospectively collected. Results. In total, 20 patients were analyzed. Of these, six patients (35%) required the positioning of a temporary tracheostomy. The functional larynx preservation rate was 95%. Females had a higher risk of both endoscopic intervention and chondronecrosis, while the median age was significantly higher in patients requiring enteral nutrition. The incidence of long-term severe toxicities was lower in patients treated with IMRT than in the historical 3D-CRT cohort. Patients who had received PORT-IMRT achieved a lower rate of permanent laryngeal and swallowing dysfunctions. Overall, results from the comparison with the historical 3D-CRT cohort favor the IMRTs. [ABSTRACT FROM AUTHOR]

Background: Breast-conserving surgery (BCS) and whole breast radiation therapy (WBRT) are the standard of care for early-stage breast cancer (BC). Based on the observation that most local recurrences occurred near the tumor bed, accelerated partial breast irradiation (APBI), consisting of a higher dose per fraction to the tumor bed over a reduced treatment time, has been gaining ground as an attractive alternative in selected patients with low-risk BC. Although more widely delivered in postoperative setting, preoperative APBI has also been investigated in a limited, though increasing, and number of studies. The aim of this study is to test the feasibility, safety and efficacy of preoperative radiotherapy (RT) in a single fraction for selected BC patients.Methods: This is a phase I/II, single-arm and open-label single-center clinical trial using CyberKnife. The clinical investigation is supported by a preplanning section which addresses technical and dosimetric issues. The primary endpoint for the phase I study, covering the 1st and 2nd year of the research project, is the identification of the maximum tolerated dose (MTD) which meets a specific target toxicity level (no grade 3-4 toxicity). The primary endpoint for the phase II study (3rd to 5th year) is the evaluation of treatment efficacy measured in terms of pathological complete response rate.Discussion: The study will investigate the response of BC to the preoperative APBI from different perspectives. While preoperative APBI represents a form of anticipated boost, followed by WBRT, different are the implications for the scientific community. The study may help to identify good responders for whom surgery could be omitted. It is especially appealing for patients unfit for surgery due to advanced age or severe co-morbidities, in addition to or instead of systemic therapies, to ensure long-term local control. Moreover, patients with oligometastatic disease synchronous with primary BC may benefit from APBI on the intact tumor in terms of tumor progression free survival. The study of response to RT can provide useful information about BC radiobiology, immunologic reactions, genomic expression, and radiomics features, to be tested on a larger scale.Trial Registration: The study was prospectively registered at clinicaltrials.gov ( NCT04679454 ). [ABSTRACT FROM AUTHOR]

• Contouring variability is a well-known issue in breast cancer radiotherapy. • Dosimetric impact of contouring variability of axillary nodes is scarcely investigated. • Variations in dosimetric coverage of axillary nodes emerged from a multicentric study. • The use of intensity modulated radiotherapy has amplified the dosimetric variations. • Consensus, quality assurance programme and automated outlining techniques are encouraged. To quantify the dosimetric impact of contouring variability of axillary lymph nodes (L2, L3, L4) in breast cancer (BC) locoregional radiotherapy (RT). 18 RT centres were asked to plan a locoregional treatment on their own planning target volume (single centre, SC-PTV) which was created by applying their institutional margins to the clinical target volume of the axillary nodes of three BC patients (P1, P2, P3) previously delineated (SC-CTV). The gold standard CTVs (GS-CTVs) of P1, P2 and P3 were developed by BC experts' consensus and validated with STAPLE algorithm. For each participating centre, the GS-PTV of each patient was created by applying the same margins as those used for the SC-CTV to SC-PTV expansion and replaced the SC-PTV in the treatment plan. Datasets were imported into MIM v6.1.7 [MIM Software Inc.], where dose-volume histograms (DVHs) were extracted and differences were analysed. 17/18 centres used intensity-modulated RT (IMRT). The CTV to PTV margins ranged from 0 to 10 mm (median 5 mm). No correlation was observed between GS-CTV coverage by 95% isodose and GS-PTV margins width. Doses delivered to 98% (D98) and 95% (D95) of GS-CTVs were significantly lower than those delivered to the SC-CTVs. No significant difference between SC-CTV and GS-CTV was observed in maximum dose (D2), always under 110%. Mean dose ≥99% of the SC-CTVs and GS-CTVs was satisfied in 84% and 50%, respectively. In less than one half of plans, GS-CTV V95% was above 90%. Breaking down the GS-CTV into the three nodal levels (L2, L3 and L4), L4 had the lowest probability to be covered by the 95% isodose. Overall, GS-CTV resulted worse coverage, especially for L4. IMRT was largely used and CTV-to-PTV margins did not compensate for contouring issues. The results highlighted the need for delineation training and standardization. [ABSTRACT FROM AUTHOR]

Purpose : Evaluation of target coverage and verification of safety margins, in motion management strategies implemented by Lung Optimized Treatment (LOT) module in CyberKnife system. Methods: Three fiducial‐less motion management strategies provided by LOT can be selected according to tumor visibility in the X ray images acquired during treatment. In 2‐view modality the tumor is visible in both X ray images and full motion tracking is performed. In 1‐view modality the tumor is visible in a single X ray image, therefore, motion tracking is combined with an internal target volume (ITV)‐based margin expansion. In 0‐view modality the lesion is not visible, consequently the treatment relies entirely on an ITV‐based approach. Data from 30 patients treated in 2‐view modality were selected providing information on the three‐dimensional tumor motion in correspondence to each X ray image. Treatments in 1‐view and 0‐view modalities were simulated by processing log files and planning volumes. Planning target volume (PTV) margins were defined according to the tracking modality: end‐exhale clinical target volume (CTV) + 3 mm in 2‐view and ITV + 5 mm in 0‐view. In the 1‐view scenario, the ITV encompasses only tumor motion along the non‐visible direction. Then, non‐uniform ITV to PTV margins were applied: 3 mm and 5 mm in the visible and non‐visible direction, respectively. We defined the coverage of each voxel of the CTV as the percentage of X ray images where such voxel was included in the PTV. In 2‐view modality coverage was calculated as the intersection between the CTV centred on the imaged target position and the PTV centred on the predicted target position, as recorded in log files. In 1‐view modality, coverage was calculated as the intersection between the CTV centred on the imaged target position and the PTV centred on the projected predictor data. In 0‐view modality coverage was calculated as the intersection between the CTV centred on the imaged target position and the non‐moving PTV. Similar to dose‐volume histogram, CTV coverage‐volume histograms (defined as CVH) were derived for each patient and treatment modality. The geometric coverages of the 90% and 95% of CTV volume (C90, C95, respectively) were evaluated. Patient‐specific optimal margins (ensuring C95 ≥ 95%) were computed retrospectively. Results: The median ± interquartile‐rage of C90 and C95 for upper lobe lesions was 99.1 ± 0.6% and 99.0 ± 3.1%, whereas they were 98.9 ± 4.2% and 97.8 ± 7.5% for lower and middle lobe tumors. In 2‐view, 1‐view and 0‐view modality, adopted margins ensured C95 ≥ 95% in 70%, 85% and 63% of cases and C95 ≥ 90% in 90%, 88% and 83% of cases, respectively. In 2‐view, 1‐view and 0‐view a reduction in margins still ensured C95 ≥ 95% in 33%, 78% and 59% of cases, respectively. Conclusions: CTV coverage analysis provided an a‐posteriori evaluation of the treatment geometric accuracy and allowed a quantitative verification of the adequacy of the PTV margins applied in CyberKnife LOT treatments offering guidance in the selection of CTV margins. [ABSTRACT FROM AUTHOR]

[Display omitted] • Using different platforms for radiomic extraction affects models' performance. • Variables' relevance is inconsistent among platforms. • MRI features are correlated to radiosurgery response in brain metastases from NSCLC. • Higher number of radiomic features does not necessarily imply better performance. Radiomics enables the mining of quantitative features from medical images. The influence of the radiomic feature extraction software on the final performance of models is still a poorly understood topic. This study aimed to investigate the ability of radiomic features extracted by two different radiomic platforms to predict clinical outcomes in patients treated with radiosurgery for brain metastases from non-small cell lung cancer. We developed models integrating pre-treatment magnetic resonance imaging (MRI)-derived radiomic features and clinical data. Pre-radiotherapy gadolinium enhanced axial T1-weighted MRI scans were used. MRI images were re-sampled, intensity-shifted, and histogram-matched before radiomic extraction by means of two different platforms (PyRadiomics and SOPHiA Radiomics). We adopted LASSO Cox regression models for multivariable analyses by creating radiomic, clinical, and combined models using three survival clinical endpoints (local control, distant progression, and overall survival). The statistical analysis was repeated 50 times with different random seeds and the median concordance index was used as performance metric of the models. We analysed 276 metastases from 148 patients. The use of the two platforms resulted in differences in both the quality and the number of extractable features. That led to mismatches in terms of end-to-end performance, statistical significance of radiomic scores, and clinical covariates found significant in combined models. This study shed new light on how extracting radiomic features from the same images using two different platforms could yield several discrepancies. That may lead to acute consequences on drawing conclusions, comparing results across the literature, and translating radiomics into clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: A planning study was performed to evaluate RapidArc (RA), a volumetric modulated arc technique, on malignant pleural mesothelioma. The benchmark was conventional fixed-field intensity-modulated radiotherapy (IMRT). Methods and materials: The computed tomography data sets of 6 patients were included. The plans for IMRT with nine fixed beams were compared against double-modulated arcs with a single isocenter. All plans were optimized for 15-MV photon beams. The dose prescription was 54 Gy to the planning target volume. The planning objectives for the planning target volume were a minimal dose of >95% and maximal dose of <107%. For the organs at risk, the parameters were as follows: contralateral lung, percentage of volume receiving 5 Gy (V5Gy) <60%, V20Gy < 10%, mean <10.0 Gy; liver, V30Gy <33%, mean <31 Gy; heart, V45Gy <30%, V50Gy <20%, dose received by 1% of the volume (D1%) <60 Gy; contralateral kidney, V15Gy <20%; spine, D1% <45 Gy; esophagus, V55Gy <30%; and spleen, V40Gy <50%. The monitor units (MUs) and delivery time were scored to measure the treatment efficiency. The pretreatment portal dosimetry scored delivery to the calculation agreement with the Gamma Agreement Index. Results: RA and IMRT provided equivalent coverage and homogeneity. Both techniques fulfilled objectives on organs at risk with a tendency of RA to improve sparing. The conformity index was 1.9 ± 0.1 for RA and IMRT. The number of MU/2Gy was 734 ± 82 for RA and 2,195 ± 317 for IMRT. The planning vs. delivery agreement revealed a Gamma Agreement Index for IMRT of 96.0% ± 2.6% and for RA of 95.7% ± 1.5%. The treatment time was 3.7 ± 0.3min for RA and 13.4 ± 0.1min for IMRT. Conclusion: RA demonstrated compared with conventional IMRT, similar target coverage and better dose sparing to the organs at risks. The number of MUs and the time required to deliver a 2-Gy fraction were much lower for RA, allowing the possibility to incorporate this technique in the treatment options for mesothelioma patients. [Copyright &y& Elsevier]

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

Purpose: A planning study was performed comparing volumetric modulated arcs, RapidArc (RA), fixed beam IMRT (IM), and conformal radiotherapy (CRT) with multiple static fields or short conformal arcs in a series of patients treated with hypofractionated stereotactic body radiation therapy (SBRT) for solitary or oligo-metastases from different tumors to abdominal lymph nodes. Methods and Materials: Fourteen patients were included in the study. Dose prescription was set to 45 Gy (mean dose to clinical target volume [CTV]) in six fractions of 7.5 Gy. Objectives for CTV and planning target volume (PTV) were as follows: Dosemin >95%, Dosemax <107%. For organs at risk the following objectives were used: Maximum dose to spine <18 Gy; V15Gy <35% for both kidneys, V36Gy <1% for duodenum, V36Gy <3% for stomach and small bowel, V15Gy <(total liver volume − 700 cm3) for liver. Dose–volume histograms were evaluated to assess plan quality. Results: Planning objectives on CTV and PTV were achieved by all techniques. Use of RA improved PTV coverage (V95% = 90.2% ± 5.2% for RA compared with 82.5% ± 9.6% and 84.5% ± 8.2% for CRT and IM, respectively). Most planning objectives for organs at risk were met by all techniques except for the duodenum, small bowel, and stomach, in which the CRT plans exceeded the dose/volume constraints in some patients. The MU/fraction values were as follows: 2186 ± 211 for RA, 2583 ± 699 for IM, and 1554 ± 153 for CRT. Effective treatment time resulted as follows: 3.7 ± 0.4 min for RA, 10.6 ± 1.2 min for IM, and 6.3 ± 0.5 min for CRT. Conclusions: Delivery of SBRT by RA showed improvements in conformal avoidance with respect to standard conformal irradiation. Delivery parameters confirmed logistical advantages of RA, particularly compared with IM. [Copyright &y& Elsevier]

To determine interobserver variability in axillary nodal contouring in breast cancer (BC) radiotherapy (RT) by comparing the clinical target volume of participating single centres (SC-CTV) with a gold-standard CTV (GS-CTV). The GS-CTV of three patients (P1, P2, P3) with increasing complexity was created in DICOM format from the median contour of axillary CTVs drawn by BC experts, validated using the simultaneous truth and performance-level estimation and peer-reviewed. GS-CTVs were compared with the correspondent SC-CTVs drawn by radiation oncologists, using validated metrics and a total score (TS) integrating all of them. Eighteen RT centres participated in the study. Comparative analyses revealed that, on average, the SC-CTVs were smaller than GS-CTV for P1 and P2 (by −29.25% and −27.83%, respectively) and larger for P3 (by +12.53%). The mean Jaccard index was greater for P1 and P2 compared to P3, but the overlap extent value was around 0.50 or less. Regarding nodal levels, L4 showed the highest concordance with the GS. In the intra-patient comparison, L2 and L3 achieved lower TS than L4. Nodal levels showed discrepancy with GS, which was not statistically significant for P1, and negligible for P2, while P3 had the worst agreement. DICE similarity coefficient did not exceed the minimum threshold for agreement of 0.70 in all the measurements. Substantial differences were observed between SC- and GS-CTV, especially for P3 with altered arm setup. L2 and L3 were the most critical levels. The study highlighted these key points to address. The present study compares, by means of validated geometric indexes, manual segmentations of axillary lymph nodes in breast cancer from different observers and different institutions made on radiotherapy planning CT images. Assessing such variability is of paramount importance, as geometric uncertainties might lead to incorrect dosimetry and compromise oncological outcome. [ABSTRACT FROM AUTHOR]