Fully automated volumetric modulated arc therapy technique for radiation therapy of locally advanced breast cancer.

BACKGROUND: This study aimed to evaluate an a-priori multicriteria plan optimization algorithm (mCycle) for locally advanced breast cancer radiation therapy (RT) by comparing automatically generated VMAT (Volumetric Modulated Arc Therapy) plans (AP-VMAT) with manual clinical Helical Tomotherapy (HT) plans. METHODS: The study included 25 patients who received postoperative RT using HT. The patient cohort had diverse target selections, including both left and right breast/chest wall (CW) and III-IV node, with or without internal mammary node (IMN) and Simultaneous Integrated Boost (SIB). The Planning Target Volume (PTV) was obtained by applying a 5 mm isotropic expansion to the CTV (Clinical Target Volume), with a 5 mm clip from the skin. Comparisons of dosimetric parameters and delivery/planning times were conducted. Dosimetric verification of the AP-VMAT plans was performed. RESULTS: The study showed statistically significant improvements in AP-VMAT plans compared to HT for OARs (Organs At Risk) mean dose, except for the heart and ipsilateral lung. No significant differences in V95% were observed for PTV breast/CW and PTV III-IV, while increased coverage (higher V95%) was seen for PTV IMN in AP-VMAT plans. HT plans exhibited smaller values of PTV V105% for breast/CW and III-IV, with no differences in PTV IMN and boost. HT had an average (± standard deviation) delivery time of (17 ± 8) minutes, while AP-VMAT took (3 ± 1) minutes. The average γ passing rate for AP-VMAT plans was 97%±1%. Planning times reduced from an average of 6 h for HT to about 2 min for AP-VMAT. CONCLUSIONS: Comparing AP-VMAT plans with clinical HT plans showed similar or improved quality. The implementation of mCycle demonstrated successful automation of the planning process for VMAT treatment of locally advanced breast cancer, significantly reducing workload.

Preoperative single fraction breast radiotherapy: Intra-fraction geometric uncertainties and dosimetric implications.

PURPOSE: A preoperative breast robotic radiosurgery trial was concluded in our centre. Purposes of the present study were to evaluate retrospectively over the enrolled patients: i) respiratory patterns ii) tracking uncertainties iii) necessity of respiratory compensation iv) tracking errors dosimetric effects. METHODS: 22 patients were treated in 21 Gy single fraction using CyberKnife (CK) respiratory modelling and tracking (SynchronyResp) and data extracted from log-files. Respiratory motion and baseline drifts (BD) were analyzed. SynchronyResp uncertainties were computed and compared with errors simulated for CK fiducial tracking without respiratory compensation. Plans were perturbed by tracking errors and perturbed doses calculated on the planning CT scan in order to simulate the dosimetric consequences of intra-fraction errors. RESULTS: After BD correction, respiratory amplitudes were below 5.5 mm except one value of 8 mm. 50% of patients showed BD above 3 mm. Standard deviations of SynchronyResp errors remained within 2.1 mm. Standard deviations of tracking errors without respiratory compensation were comparable and below 2.5 mm. Using a 3 mm PTV margin, perturbed CTV coverage was below 95% (93.7%) just for one patient. The latter case presented a large CTV-Skin interface. Perturbed OAR doses were always judged clinically acceptable. CONCLUSION: Intra-fraction geometric uncertainties and their effects were quantified for breast neoadjuvant CK treatments. Data indicated that in the majority of cases respiratory compensation may be disabled without increasing uncertainties and reducing treatment time, provided that fiducial intra-fraction tracking is performed to account for BD. Dosimetric effects are mostly not clinically relevant.

Durvalumab with cetuximab and radiotherapy for locally advanced squamous cell carcinoma of the head and neck: A phase 1/2 trial.

BACKGROUND AND PURPOSE: To report on the anti-tumor activity of a novel combination in high-risk locally advanced head and neck squamous cell carcinoma. MATERIALS AND METHODS: At a fixed dose of 1500 mg every 28 days, anti PD-L1 Durvalumab was given concomitantly to Radiotherapy and Cetuximab starting from the first week of combined treatment, followed by adjuvant Durvalumab to a maximum of 6 months after completion of radiation. The primary endpoint of the study was 2-year progression-free survival (PFS). A safety run-in was planned. Due to regulatory issues which prevented from opening multiple centers, COVID-19 pandemic and withdrawal of Durvalumab from supporting company, the study was prematurely terminated in April 2021. RESULTS: Between July 2019 and August 2020, 9 patients were enrolled in the study. All tumors had a PD-L1 Combined Positive Score > 1. Optimal drug exposure was observed, with mean relative dose intensity of 85.5% and 87.5% for Cetuximab and Durvalumab, respectively. No radiation breaks were necessary. A grade 4 mucositis lasting for 14 days corresponded to the only dose limiting toxicity we reported. At a median follow-up of 11.5 months (IQR 7.7-16.7) all surviving patients (6 out of 9) are disease-free, with 1 and 2-year PFS rates of 77.7% and 58.3%, respectively. A selective sparing of node levels in the elective volume was performed in all cases, yielding a cumulative mean dose of 37.6 Gy (SD 8.4). CONCLUSION: Albeit limited by the small sample size, our preliminary observation of anti-tumor activity and tolerability of Durvalumab in addition to Cetuximab and radiation may warrant further investigations.

A multiparametric method to assess the MIM deformable image registration algorithm.

A quantitative evaluation of the performances of the deformable image registration (DIR) algorithm implemented in MIM-Maestro was performed using multiple similarity indices. Two phantoms, capable of mimicking different anatomical bending and tumor shrinking were built and computed tomography (CT) studies were acquired after applying different deformations. Three different contrast levels between internal structures were artificially created modifying the original CT values of one dataset. DIR algorithm was applied between datasets with increasing deformations and different contrast levels and manually refined with the Reg Refine tool. DIR algorithm ability in reproducing positions, volumes, and shapes of deformed structures was evaluated using similarity indices such as: landmark distances, Dice coefficients, Hausdorff distances, and maximum diameter differences between segmented structures. Similarity indices values worsen with increasing bending and volume difference between reference and target image sets. Registrations between images with low contrast (40 HU) obtain scores lower than those between images with high contrast (970 HU). The use of Reg Refine tool leads generally to an improvement of similarity parameters values, but the advantage is generally less evident for images with low contrast or when structures with large volume differences are involved. The dependence of DIR algorithm on image deformation extent and different contrast levels is well characterized through the combined use of multiple similarity indices.

SBRT planning for spinal metastasis: indications from a large multicentric study.

BACKGROUND: The dosimetric variability in spine stereotactic body radiation therapy (SBRT) planning was investigated in a large number of centres to identify crowd knowledge-based solutions. METHODS: Two spinal cases were planned by 48 planners (38 centres). The required prescription dose (PD) was 3â€¯× 10 Gy and the planning target volume (PTV) coverage request was: VPD > 90% (minimum request: VPD > 80%). The dose constraints were: planning risk volume (PRV) spinal cord: V18Gy < 0.35 cm3, V21.9 Gy < 0.03 cm3; oesophagus: V17.7 Gy < 5 cm3, V25.2 Gy < 0.03 cm3. Planners who did not fulfil the protocol requirements were asked to re-optimize the plans, using the results of planners with the same technology. Statistical analysis was performed to assess correlations between dosimetric results and planning parameters. A quality index (QI) was defined for scoring plans. RESULTS: In all, 12.5% of plans did not meet the protocol requirements. After re-optimization, 98% of plans fulfilled the constraints, showing the positive impact of knowledge sharing. Statistical analysis showed a significant correlation (p < 0.05) between the homogeneity index (HI) and PTV coverage for both cases, while the correlation between HI and spinal cord sparing was significant only for the single dorsal PTV case. Moreover, the multileaf collimator leaf thickness correlated with the spinal cord sparing. Planners using comparable delivery/planning system techniques produced different QI, highlighting the impact of the planner's skills in the optimization process. CONCLUSION: Both the technology and the planner's skills are fundamentally important in spine SBRT planning optimization. Knowledge sharing helped to follow the plan objectives.

CyberKnife MLC-based treatment planning for abdominal and pelvic SBRT: Analysis of multiple dosimetric parameters, overall scoring index and clinical scoring.

PURPOSE: This study evaluated the plan quality of CyberKnife MLC-based treatment planning in comparison to the Iris collimator for abdominal and pelvic SBRT. Multiple dosimetric parameters were considered together with a global scoring index validated by clinical scoring. METHODS AND MATERIALS: Iris and MLC plans were created for 28 liver, 15 pancreas and 13 prostate cases including a wide range of PTV sizes (24-643 cm3). Plans were compared in terms of coverage, conformity (nCI), dose gradient (R50%), homogeneity (HI), OAR doses, PTV gEUD, MU, treatment time both estimated by TPS (tTPS) and measured. A global plan quality score index was calculated for IRIS and MLC solutions and validated by a clinical score given independently by two observers. RESULTS: Compared to Iris, MLC achieved equivalent coverage and conformity without compromising OAR sparing and improving R50% (p < 0.001). MLC gEUD was slightly lower than Iris (p < 0.05) for abdominal cases. MLC reduced significantly MU (-15%) and tTPS (-22%). Time reduction was partially lost when measured. The global score index was significantly higher for MLC solutions which were selected in 73% and 64% of cases respectively by the first and second observer. CONCLUSION: Iris and MLC comparison was not straightforward when based on multiple dosimetric parameters. The use of a mathematical overall score index integrated with a clinical scoring was essential to confirm MLC plans advantages over Iris solutions.

Stereotactic Body Radiotherapy in Patients with Lung Oligometastases from Colorectal Cancer.

AIM: To assess the role of stereotactic body radiotherapy (SBRT) in pulmonary metastases from colorectal cancer (CRC). PATIENTS AND METHODS: Thirty-three consecutive patients with pulmonary metastases from CRC who received SBRT were included in the analysis. The primary endpoints were local and systemic progression-free survival, a secondary endpoint was the safety profile of SBRT. RESULTS: A total of 56 lesions were treated with SBRT. A single nodule was treated in 15 patients, two in 13 and three in five. The radiotherapy dose and the adopted fractionations were 24-27 Gy as a single fraction for 40 lesions and 27-42 Gy in three fractions (2-3 times a week) for the other 16 lesions. After a median follow-up of 22.8 months (range=1.3-45.7 months), the median progression-free survival of the irradiated sites was 13.4 months. CONCLUSION: SBRT can be considered as local therapy in patients with lung metastases from CRC.

In phantom assessment of superficial doses under TomoTherapy irradiation.

PURPOSE: Aim of this work is the assessment of build-up and superficial doses of different clinical Head&Neck plans delivered with Helical TomoTherapy (HT) (Accuray, Sunnyvale, CA). Depth dose profiles and superficial dose points were measured in order to evaluate the Treatment Planning System (TPS) capability of an accurate dose modeling in regions of disequilibrium. Geometries and scattering conditions were investigated, similar to the ones generally encountered in clinical treatments. METHODS: Measurements were performed with two dosimeters: Gafchromic® EBT3 films (Ashland Inc., Wayne, NJ) and a synthetic single crystal diamond detector (PTW-Frieburg microDiamond, MD). A modified version of the Alderson RANDO phantom was employed to house the detectors. A comparison with TPS data was carried out in terms of dose difference (DD) and distance-to-agreement (DTA). RESULTS: DD between calculated data and MD measurements are within 4% even in points with high spatial dose variation. For depth profiles, EBT3 data show a DDmax of 3.3% and DTAmax of 2.2mm, in low and high gradient regions, respectively, and compare well with MD data. EBT3 superficial points always results in measured doses lower than TPS evaluated ones, with a maximum DTA value of 1.5mm. CONCLUSIONS: Doses measured with the two devices are in good agreement and compare well with calculated data. The deviations found in the present work are within the reference tolerance level, suggesting that the HT TPS is capable of a precise dose estimation both in superficial regions and in correspondence with interfaces between air and PMMA.

GafChromic(®) EBT3 films for patient specific IMRT QA using a multichannel approach.

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.

Four-dimensional computed tomography in accelerated partial breast irradiation planning: single series from a phase III trial.

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.

Comparison of stereotactic plans for brain tumors with two different multileaf collimating systems.

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.

A synthetic diamond diode in volumetric modulated arc therapy dosimetry.

PURPOSE: The aim of this work is to investigate the behavior of a single crystal diamond diode (SCDD) for volumetric modulated arc therapy (VMAT) dose verifications. This delivery technique is one of the most severe test of a dosimeter performance due to the modulation of the dose rate achieved by simultaneously changing the velocity of the gantry and the position of the collimator leaves. The performed measurements with VMAT photon beams can therefore contribute to an overall global validation of the device to be used in dose distribution verifications. METHODS: The SCDD response to 6 MVRX has been tested and compared with reference ionization chambers and treatment planning system (TPS) calculations in different experiments: (a) measurements of output factors for small field sizes (square fields of side ranging between 8 mm and 104 mm) by SCDD and A1SL ionization chamber; (b) angular dependence evaluation of the entire experimental set-up by SCDD, A1SL, and Farmer ionization chambers; and (c) acquisition of dose profiles for a VMAT treatment of a pulmonary disease in latero-lateral and gantry-target directions by SCDD and A1SL ionization chamber. RESULTS: The output factors measured by SCDD favorably compare with the ones obtained by A1SL, whose response is affected by the lack of charged particle equilibrium and by averaging effect when small fields are involved. From the experiment on angular dependence, a good agreement is observed among the diamond diode, the ion chambers, and the TPS. In VMAT profiles, the absorbed doses measured by SCDD and A1SL compare well with the TPS calculated ones. An overall better agreement is observed in the case of the diamond dosimeter, which is also showing a better accuracy in terms of distance to agreement in the high gradient regions. CONCLUSIONS: Synthetic diamond diodes, whose performance were previously studied for conformal and IMRT radiotherapy techniques, were found to be suitable detectors also for dosimetric measurements in volumetric arc therapy treatments.