Mixed-Beam Approach for High-Risk Prostate Cancer Carbon-Ion Boost Followed by Photon Intensity-Modulated Radiotherapy: Preliminary Results of Phase II Trial AIRC-IG-14300.

PURPOSE: This study represents a descriptive analysis of preliminary results of a Phase II trial on a novel mixed beam radiotherapy (RT) approach, consisting of carbon ions RT (CIRT) followed by intensity-modulated photon RT, in combination with hormonal therapy, for high-risk prostate cancer (HR PCa) with a special focus on acute toxicity. METHODS: Primary endpoint was the evaluation of safety in terms of acute toxicity. Secondary endpoints were early and long-term tolerability of treatment, quality of life (QoL), and efficacy. Data on acute and late toxicities were collected according to RTOG/EORTC. QoL of enrolled patients was assessed by IPSS, EORTC QLQ-C30, EORTC QLQ-PR25, and sexual activity by IIEF-5. RESULTS: Twenty-six patients were enrolled in the study, but only 15 completed so far the RT course and were included. Immediately after CIRT, no patients experienced GI/GU toxicity. At 1 and 3 months from the whole course RT completion, no GI/GU toxicities greater than grade 2 were observed. QoL scores were overall satisfactory. CONCLUSIONS: The feasibility of the proposed mixed treatment schedule was assessed, and an excellent acute toxicity profile was recorded. Such findings instil confidence in the continuation of this mixed approach, with evaluation of long-term tolerability and efficacy.

Dosimetric Impact of Inter-Fraction Anatomical Changes in Carbon Ion Boost Treatment for High-Risk Prostate Cancer (AIRC IG 14300).

Rectum and bladder volumes play an important role in the dose distribution reproducibility in prostate cancer adenocarcinoma (PCa) radiotherapy, especially for particle therapy, where density variation can strongly affect the dose distribution. We investigated the reliability and reproducibility of our image-guided radiotherapy (IGRT) and treatment planning protocol for carbon ion radiotherapy (CIRT) within the phase II mixed beam study (AIRC IG 14300) for the treatment of high-risk PCa. In order to calculate the daily dose distribution, a set of synthetic computed tomography (sCT) images was generated from the cone beam computed tomography (CBCT) images acquired in each treatment session. Planning target volume (PTV) together with rectum and bladder volume variation was evaluated with sCT dose-volume histogram (DVH) metric deviations from the planning values. The correlations between the bladder and rectum volumes, and the corresponding DVH metrics, were also assessed. No significant difference in the bladder, rectum, and PTV median volumes between the planning computed tomography (pCT) and the sCT was found. In addition, no significant difference was assessed when comparing the average DVHs and median DVH metrics between pCT and sCT. Dose deviations determined by bladder and rectum filling variations demonstrated that dose distributions were reproducible in terms of both target coverage and organs at risk (OARs) sparing.

Convolutional Neural Networks Cascade for Automatic Pupil and Iris Detection in Ocular Proton Therapy.

Eye tracking techniques based on deep learning are rapidly spreading in a wide variety of application fields. With this study, we want to exploit the potentiality of eye tracking techniques in ocular proton therapy (OPT) applications. We implemented a fully automatic approach based on two-stage convolutional neural networks (CNNs): the first stage roughly identifies the eye position and the second one performs a fine iris and pupil detection. We selected 707 video frames recorded during clinical operations during OPT treatments performed at our institute. 650 frames were used for training and 57 for a blind test. The estimations of iris and pupil were evaluated against the manual labelled contours delineated by a clinical operator. For iris and pupil predictions, Dice coefficient (median = 0.94 and 0.97), Szymkiewicz-Simpson coefficient (median = 0.97 and 0.98), Intersection over Union coefficient (median = 0.88 and 0.94) and Hausdorff distance (median = 11.6 and 5.0 (pixels)) were quantified. Iris and pupil regions were found to be comparable to the manually labelled ground truths. Our proposed framework could provide an automatic approach to quantitatively evaluating pupil and iris misalignments, and it could be used as an additional support tool for clinical activity, without impacting in any way with the consolidated routine.

Mixed-beam approach in locally advanced nasopharyngeal carcinoma: IMRT followed by proton therapy boost versus IMRT-only. Evaluation of toxicity and efficacy.

Objective: To compare radiation-induced toxicity and dosimetry parameters in patients with locally advanced nasopharyngeal cancer (LANPC) treated with a mixed-beam (MB) approach (IMRT followed by proton therapy boost) with an historic cohort of patients treated with a full course of IMRT-only.Material and methods: Twenty-seven patients with LANPC treated with the MB approach were compared to a similar cohort of 17 patients treated with IMRT-only. The MB approach consisted in a first phase of IMRT up to 54-60 Gy followed by a second phase delivered with a proton therapy boost up to 70-74 Gy (RBE). The total dose for patients treated with IMRT-only was 69.96 Gy. Induction chemotherapy was administrated to 59 and 88% and concurrent chemoradiotherapy to 88 and 100% of the MB and IMRT-only patients, respectively. The worst toxicity occurring during the entire course of treatment (acute toxicity) and early-late toxicity were registered according to the Common Terminology Criteria Adverse Events V4.03.Results: The two cohorts were comparable. Patients treated with MB received a significantly higher median total dose to target volumes (p = .02). Acute grade 3 mucositis was found in 11 and 76% (p = .0002) of patients treated with MB and IMRT-only approach, respectively, while grade 2 xerostomia was found in 7 and 35% (p = .02) of patients treated with MB and IMRT-only, respectively. There was no statistical difference in late toxicity. Local progression-free survival (PFS) and progression-free survival curves were similar between the two cohorts of patients (p = .17 and p = .40, respectively). Local control rate was 96% and 81% for patients treated with MB approach and IMRT-only, respectively.Conclusions: Sequential MB approach for LANPC patients provides a significantly lower acute toxicity profile compared to full course of IMRT. There were no differences in early-late morbidities and disease-related outcomes (censored at two-years) but a longer follow-up is required to achieve conclusive results.

Workload of breast image-guided intensity-modulated radiotherapy delivered with TomoTherapy.

OBJECTIVE: To report treatment times (door to door) of adjuvant treatments of breast cancer (BC) with intensity-modulated radiotherapy (IMRT). METHODS: Treatment times of 62 patients with BC on the TomoTherapy Hi-Art System were collected for the analysis. Patients underwent either locoregional radiotherapy (postmastectomy radiotherapy [PMRT]) with helical modality (TomoHelical) or whole breast radiotherapy (RT) with simultaneous integrated boost (WBRT-SIB) with direct modality (TomoDirect). Door-to-door time was broken down into different steps, which were crucial to RT session. RESULTS: A total of 594 treatment fractions were monitored. Median treatment time was 22.4 minutes (17.2-30.8) for PMRT and 14.4 minutes (10.9-23.5) for WBRT-SIB. The mean beam-on time accounted for 61.36% of the overall treatment time for PMRT compared to 57% for WBRT-SIB. The beam-on time was a much more time-consuming process. CONCLUSION: This treatment times analysis on the use of IMRT for BC might be useful to organize and improve the workflow efficiency in RT facilities.

Long-time clinical experience in patient setup for several particle therapy clinical indications: management of patient positioning and evaluation of setup reproducibility and stability.

OBJECTIVE: Accurate patient positioning is crucial in particle therapy due to the geometrical selectivity of particles. We report and discuss the National Center for Oncological Hadrontherapy (CNAO) experience in positioning accuracy and stability achieved with solid thermoplastic masks fixed on index base plates and assessed by daily orthogonal X-ray imaging. METHODS: Positioning data were retrospectively collected (between 2012 and 2018) and grouped according to the treated anatomical site. 19696 fractions of 1325 patients were evaluated.The study was designed to assess:(i) the number of fractions in which a single correction vector was applied(SCV);(ii) the number of fractions in which further setup verification was performed (SV);(iii) the number of fractions in which SV lead to an additional correction within (MCV<5min) or after (MCV>5min) 5 minutes from the first setup correction;(iv) the systematic (Σ) and random (σ) error components of the correction vectors applied. RESULTS: A SCV was applied in 71.5% of fractions, otherwise SV was required. In 30.6% of fractions with SV, patient position was not further revised. In the remaining fractions, MCV<5min and MCV>5min were applied mainly in extracranial and cranial sites respectively.Interfraction Σ was ≤ 1.7 mm/0.7° and σ was ≤ 1.2 mm/0.6° in cranial sites while in extracranial sites Σ was ≤ 5.5 mm/0.9° and σ was ≤4.4 mm/0.9°. Setup residuals were submillimetric in all sites. In cranial patients, maximum intrafractional Σ was 0.8 mm/0.4°. CONCLUSION: This report extensively quantifies inter- and intrafraction setup accuracy on an institutional basis and confirms the need of image guidance to fully benefit from the geometrical selectivity of particles. ADVANCES IN KNOWLEDGE: The reported analysis provides a board institutional data set on the evaluation of patient immobilization and bony anatomy alignment for several particle therapy clinical indications.

A platform for patient positioning and motion monitoring in ocular proton therapy with a non-dedicated beamline.

PURPOSE: At Centro Nazionale di Adroterapia Oncologica (CNAO, Pavia, Italy) ocular proton therapy (OPT) is delivered using a non-dedicated beamline. This paper describes the novel clinical workflow as well as technologies and methods adopted to achieve accurate target positioning and verification during ocular proton therapy at CNAO. METHOD: The OPT clinical protocol at CNAO prescribes a treatment simulation and a delivery phase, performed in the CT and treatment rooms, respectively. The patient gaze direction is controlled and monitored during the entire workflow by means of an eye tracking system (ETS) featuring two optical cameras and an embedded fixation diode light. Thus, the accurate alignment of the fixation light provided to the patient to the prescribed gazed direction is required for an effective treatment. As such, a technological platform based on active robotic manipulators and IR optical tracking-based guidance was developed and tested. The effectiveness of patient positioning strategies was evaluated on a clinical dataset comprising twenty patients treated at CNAO. RESULTS: According to experimental testing, the developed technologies guarantee uncertainties lower than one degree in gaze direction definition by means of ETS-guided positioning. Patient positioning and monitoring strategies during treatment effectively mitigated set-up uncertainties and exhibited sub-millimetric accuracy in radiopaque markers alignment. CONCLUSION: Ocular proton therapy is currently delivered at CNAO with a non-dedicated beamline. The technologies developed for patient positioning and motion monitoring have proven to be compliant with the high geometrical accuracy required for the treatment of intraocular tumors.

Stereotactic body radiation therapy for mediastinal lymph node metastases: how do we fly in a 'no-fly zone'?

PURPOSE: To evaluate the treatment-induced toxicity (as primary endpoint) and the efficacy (as secondary endpoint) of stereotactic body radiation therapy (SBRT) in the treatment of mediastinal lymph nodes (LNs) in the so-called no-fly zone (NFZ) in cancers with various histology. MATERIAL AND METHODS: Forty-two patients were retrospectively analyzed. Institutional dose/volume constraints for organs at risk (OARs) derived by published data were strictly respected. The correlation between treatment-related variables and toxicity was investigated by logistic regression, Chi-squared test or Fisher's exact test. Overall survival (OS), cause-specific survival (CSS), progression-free survival (PFS) and local control (LC) were collected from the follow-up reports. The impact of potential predictive factors on LC, PFS and OS were estimated by Cox proportional-hazard regression. RESULTS: Median follow-up time was 16 months (range 1-41). Four patients had esophageal G1 toxicity. Ten and six patients had G1 and G2 pulmonary toxicity, respectively. Treatment site and irradiation technique were significantly correlated with G ≥ 2 and G ≥ 1 toxicity, respectively. OS probability at 19 months was 88.3% and corresponded to CSS. LC probability at 16 months was 66.3% (median LC duration: 22 months, range 1-41). Fifteen patients (35.7%) were disease-free at 25 months (median time, range 1-41). The biologically effective dose (BED) and the target dose coverage indexes were significantly correlated with LC. CONCLUSIONS: SBRT can be considered as a safe treatment option for selected patients with oligo-metastases/recurrences in the NFZ, if strict dose/volume constraints are applied.

Dosimetric study to assess the feasibility of intraoperative radiotherapy with electrons (ELIOT) as partial breast irradiation for patients with cardiac implantable electronic device (CIED).

PURPOSE: To report in-vivo dosimetry in the infraclavicular region, a potential site of a cardiac implantable electronic device (CIED) and to evaluate the absorbed dose from intraoperative radiotherapy with electrons (ELIOT). METHODS: 27 non-cardiopathic breast cancer (BC) patients without CIED received quadrantectomy and ELIOT as partial breast irradiation. Before delivering ELIOT, two catheters, each containing eight thermoluminescent dosimeters (TLDs), were positioned in the infraclavicular region. TLDs internal catheter was located deep in the tumor bed while the external catheter was placed on patient's skin. RESULTS: Data were available for 24/27 patients. The absorbed doses were referred to the dose of 21 Gy. Values measured by the external catheter were low, although statistically significant higher doses were found close to the applicator (mean values 0.26-0.49 Gy). External TLD doses in proximity of the applicator were lower than those detected by their internal counterparts. Values measured by the internal catheter TLDs varied according to the distance from the applicator while no correlation with tumor site and beam energy was found. The distance from the applicator to deliver < 2 Gy to a CIED was 2 cm, while from 2.5 cm the dose measured in all the patients became negligible. CONCLUSIONS: This dosimetric study provided data to support the clinical use of ELIOT in BC patients having CIEDs as long as the suggested minimum safe distance of 2.5 cm is taken from the RT field in case of ELIOT single dose of 21 Gy, in the energy range of 6-10 MeV.

Multi atlas based segmentation: should we prefer the best atlas group over the group of best atlases?

Multi atlas based segmentation (MABS) uses a database of atlas images, and an atlas selection process is used to choose an atlas subset for registration and voting. In the current state of the art, atlases are chosen according to a similarity criterion between the target subject and each atlas in the database. In this paper, we propose a new concept for atlas selection that relies on selecting the best performing group of atlases rather than the group of highest scoring individual atlases. Experiments were performed using CT images of 50 patients, with contours of brainstem and parotid glands. The dataset was randomly split into two groups: 20 volumes were used as an atlas database and 30 served as target subjects for testing. Classic oracle selection, where atlases are chosen by the highest dice similarity coefficient (DSC) with the target, was performed. This was compared to oracle group selection, where all the combinations of atlas subgroups were considered and scored by computing DSC with the target subject. Subsequently, convolutional neural networks were designed to predict the best group of atlases. The results were also compared with the selection strategy based on normalized mutual information (NMI). Oracle group was proven to be significantly better than classic oracle selection (p < 10-5). Atlas group selection led to a median ± interquartile DSC of 0.740 ± 0.084, 0.718 ± 0.086 and 0.670 ± 0.097 for brainstem and left/right parotid glands respectively, outperforming NMI selection 0.676 ± 0.113, 0.632 ± 0.104 and 0.606 ± 0.118 (p < 0.001) as well as classic oracle selection. The implemented methodology is a proof of principle that selecting the atlases by considering the performance of the entire group of atlases instead of each single atlas leads to higher segmentation accuracy, being even better then current oracle strategy. This finding opens a new discussion about the most appropriate atlas selection criterion for MABS.

Stereotactic body radiotherapy for castration-sensitive prostate cancer bone oligometastases.

To evaluate outcome in patients treated with stereotactic body radiotherapy (SBRT) on bone oligometastases from castration-sensitive prostate cancer after primary treatment. We retrospectively collected data of patients with less than five lesions at time of SBRT and hormone-naïve disease at the first extra-regional localization, treated between 03/2012 and 11/2016. Prostate-specific antigen (PSA) was measured every 3 months after SBRT. Imaging was performed in case of progression. Survival analysis was performed with Kaplan-Meier (log-rank test) approach. Fifty-five patients were treated on 77 bone oligometastases. Median age, initial PSA and pre-SBRT PSA were 72 years, 9.12 and 3.5 ng/mL, respectively. Twenty-five patients (45%) received SBRT alone while the remaining 30 patients (55%) received concomitant ADT. Median follow-up was 24.6 months (range 3.0-67.2 months). No acute or late toxicity of grade > 1 was reported. Clinical progression was observed in 38 (69%) patients. 1-year biochemical progression-free survival (b-PFS), clinical progression-free survival (c-PFS), prostate-specific survival (PCSS) and local control (LC) rates were 51, 56, 100 and 83%, respectively. Comparing patients treated with SBRT alone and with concomitant ADT, no significant differences were found for those outcomes. SBRT is safe and allows high 1-year LC rate (83%) with low toxicity profile. No significant improvement in outcomes was registered with the addition of ADT to SBRT.

Hypofractionated postmastectomy radiotherapy with helical tomotherapy in patients with immediate breast reconstruction: dosimetric results and acute/intermediate toxicity evaluation.

The aim of this study was to evaluate the dosimetry and toxicity of hypofractionation in postmastectomy radiotherapy (PMRT) with intensity-modulated radiotherapy (IMRT) in breast cancer (BC) patients. Stage II-III BC patients with implant-based immediate breast reconstruction received PMRT to the chest wall (CW) and to the infra/supraclavicular nodal region (NR) using a 15-fraction schedule (2.67 Gy/fraction) and helical IMRT (Tomotherapy® System, Accuray Incorporated, Sunnyvale, CA). A score was assigned to each treatment plan in terms of planning target volume (PTV) coverage of CW and NR and the sparing of the organs at risk (OARs). The total score for each plan was calculated. Toxicity was prospectively assessed according to validated scales. Data from 120 consecutive patients treated in the period 2012-2015 were analysed with a median follow-up from the end of radiotherapy of 13.2 months (range 0.0-35 months). 70.8% (85/120) of the plans had high total scores as a result of an optimal coverage of both CW and RN and optimal sparing of all OARs. The maximum acute toxicity was of grade 2 in 36.7% of the cases. Early late toxicity was mild in the majority of cases. In the study population, helical tomotherapy-based IMRT produced optimal treatment plans in most cases. Acute and late toxicity was mild/moderate. Hypofractionated helical IMRT appears to be safe and feasible in the moderate term for PMRT.

Evaluation of target coverage and margins adequacy during CyberKnife Lung Optimized Treatment.

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.

Recent advances in radiation oncology.

Radiotherapy (RT) is very much a technology-driven treatment modality in the management of cancer. RT techniques have changed significantly over the past few decades, thanks to improvements in engineering and computing. We aim to highlight the recent developments in radiation oncology, focusing on the technological and biological advances. We will present state-of-the-art treatment techniques, employing photon beams, such as intensity-modulated RT, volumetric-modulated arc therapy, stereotactic body RT and adaptive RT, which make possible a highly tailored dose distribution with maximum normal tissue sparing. We will analyse all the steps involved in the treatment: imaging, delineation of the tumour and organs at risk, treatment planning and finally image-guidance for accurate tumour localisation before and during treatment delivery. Particular attention will be given to the crucial role that imaging plays throughout the entire process. In the case of adaptive RT, the precise identification of target volumes as well as the monitoring of tumour response/modification during the course of treatment is mainly based on multimodality imaging that integrates morphological, functional and metabolic information. Moreover, real-time imaging of the tumour is essential in breathing adaptive techniques to compensate for tumour motion due to respiration. Brief reference will be made to the recent spread of particle beam therapy, in particular to the use of protons, but also to the yet limited experience of using heavy particles such as carbon ions. Finally, we will analyse the latest biological advances in tumour targeting. Indeed, the effectiveness of RT has been improved not only by technological developments but also through the integration of radiobiological knowledge to produce more efficient and personalised treatment strategies.

Multimodal image registration for the identification of dominant intraprostatic lesion in high-precision radiotherapy treatments.

PURPOSE: The integration of CT and multiparametric MRI (mpMRI) is a challenging task in high-precision radiotherapy for prostate cancer. A simple methodology for multimodal deformable image registration (DIR) of prostate cancer patients is presented. METHODS: CT and mpMRI of 10 patients were considered. Organs at risk and prostate were contoured on both scans. The dominant intraprostatic lesion was additionally delineated on MRI. After a preliminary rigid image registration, the voxel intensity of all the segmented structures in both scans except the prostate was increased by a specific amount (a constant additional value, A), in order to enhance the contrast of the main organs influencing its position and shape. 70 couples of scans were obtained by varying A from 0 to 800 and they were subsequently non-rigidly registered. Quantities derived from image analysis and contour statistics were considered for the tuning of the best performing A. RESULTS: A = 200 resulted the minimum enhancement value required to obtain statistically significant superior registration results. Mean centre of mass distance between corresponding structures decreases from 7.4 mm in rigid registration to 5.3 mm in DIR without enhancement (DIR-0) and to 2.7 mm in DIR with A = 200 (DIR-200). Mean contour distance was 2.5, 1.9 and 0.67 mm in rigid registration, DIR-0 and DIR-200, respectively. In DIR-200 mean contours overlap increases of +13 and +24% with respect to DIR-0 and rigid registration, respectively. CONCLUSION: Contour propagation according to the vector field resulting from DIR-200 allows the delineation of dominant intraprostatic lesion on CT scan and its use for high-precision radiotherapy treatment planning. Advances in knowledge: We investigated the application of a B-spline, mutual information-based multimodal DIR coupled with a simple, patient-unspecific but efficient contrast enhancement procedure in the pelvic body area, thus obtaining a robust and accurate methodology to transfer the functional information deriving from mpMRI onto a planning CT reference volume.

Comparison of Treatment Outcome Between Invasive Lobular and Ductal Carcinomas in Patients Receiving Partial Breast Irradiation With Intraoperative Electrons.

PURPOSE: To investigate the local outcome of patients after accelerated partial breast irradiation with intraoperative electrons (IORT) for invasive lobular carcinoma (ILC) compared with invasive ductal carcinoma (IDC). METHODS AND MATERIALS: From 1999 to 2007, 2173 patients were treated with breast-conserving surgery and IORT (21 Gy/1 fraction) as the sole local treatment: 252 patients with ILC (11.6%) were compared with 1921 patients with IDC in terms of local control. RESULTS: Compared with the IDC subgroup, patients with ILC had a low-risk profile and were more hormone responsive. The 5- and 10-year in-breast tumor reappearance (IBTR) rates were 5.5% and 14.4%, respectively, for the IDC group and 7.5% and 21.8%, respectively, for the ILC group (log-rank P=.03). The excess risk of IBTR associated with ILC was particularly high for small tumors (≤1 cm: hazard ratio [HR], 2.24; 95% confidence interval [CI], 1.03-4.85), elderly patients (60-69 years: HR, 2.27; 95% CI, 1.11-4.63; ≥70 years: HR, 3.28; 95% CI, 1.08-10.0), low-grade tumors (grade 1: HR, 3.50; 95% CI, 1.05-11.7), and luminal A molecular subtype (HR, 3.18; 95% CI, 1.49-6.77). Among the ILC histologic variants, no difference between classic and nonclassic subgroups was observed, although the signet ring cell and solid variants had the worst local control. CONCLUSIONS: Despite a favorable tumor profile, accelerated partial breast irradiation with IORT led to a higher incidence of IBTRs in patients with ILC compared with those with IDC. Our institutional experience emphasized the importance of the size of the irradiation field, pointing to the use of larger collimators, even when dealing with small tumors, to improve local control.

Dosimetric characterization of 3D printed bolus at different infill percentage for external photon beam radiotherapy.

BACKGROUND AND PURPOSE: 3D printing is rapidly evolving and further assessment of materials and technique is required for clinical applications. We evaluated 3D printed boluses with acrylonitrile butadiene styrene (ABS) and polylactide (PLA) at different infill percentage. MATERIAL AND METHODS: A low-cost 3D printer was used. The influence of the air inclusion within the 3D printed boluses was assessed thoroughly both with treatment planning system (TPS) and with physical measurements. For each bolus, two treatment plans were calculated with Monte Carlo algorithm, considering the computed tomography (CT) scan of the 3D printed bolus or modelling the 3D printed bolus as a virtual bolus structure with a homogeneous density. Depth dose measurements were performed with Gafchromic films. RESULTS: High infill percentage corresponds to high density and high homogeneity within bolus material. The approximation of the bolus in the TPS as a homogeneous material is satisfying for infill percentages greater than 20%. Measurements performed with PLA boluses are more comparable to the TPS calculated profiles. For boluses printed at 40% and 60% infill, the discrepancies between calculated and measured dose distribution are within 5%. CONCLUSIONS: 3D printing technology allows modulating the shift of the build-up region by tuning the infill percentage of the 3D printed bolus in order to improve superficial target coverage.

First clinical investigation of a 4D maximum likelihood reconstruction for 4D PET-based treatment verification in ion beam therapy.

BACKGROUND AND PURPOSE: In clinical applications of Positron Emission Tomography (PET)-based treatment verification in ion beam therapy (PT-PET), detection and interpretation of inconsistencies between Measured PET and Expected PET are mostly limited by Measured PET noise, due to low count statistics, and by Expected PET bias, especially due to inaccurate washout modelling in off-line implementations. In this work, a recently proposed 4D Maximum Likelihood (ML) reconstruction algorithm which considers Measured PET and Expected PET as two different motion phases of a 4D dataset is assessed on clinical 4D PET-CT datasets acquired after carbon ion therapy. MATERIAL AND METHODS: The 4D ML reconstruction algorithm estimates: (1) Measured PET of enhanced image quality with respect to the conventional Measured PET, thanks to the exploitation of Expected PET; (2) the deformation field mapping the Expected PET onto the Measured PET as a measure of the occurred displacements. RESULTS: Results demonstrate the desired sensitivity to inconsistencies due to breathing motion and/or setup modification, robustness to noise in different count statistics scenarios, but a limited sensitivity to Expected PET washout inaccuracy. CONCLUSIONS: The 4D ML reconstruction algorithm supports clinical 4D PT-PET in ion beam therapy. The limited sensitivity to washout inaccuracy can be detected and potentially overcome.

Variability in axillary lymph node delineation for breast cancer radiotherapy in presence of guidelines on a multi-institutional platform.

AIM: To quantify the variability between radiation oncologists (ROs) when outlining axillary nodes in breast cancer. MATERIAL AND METHODS: For each participating center, three ROs with different levels of expertise, i.e., junior (J), senior (S) and expert (E), contoured axillary nodal levels (L1, L2, L3 and L4) on the CT images of three different patients (P) of an increasing degree of anatomical complexity (from P1 to P2 to P3), according to contouring guidelines. Consensus contours were generated using the simultaneous truth and performance level estimation (STAPLE) method. RESULTS: Fifteen centers and 42 ROs participated. Overall, the median Dice similarity coefficient was 0.66. Statistically significant differences were observed according to the level of expertise (better agreement for J and E, worse for S); the axillary level (better agreement for L1 and L4, worse for L3); the patient (better agreement for P1, worse for P3). Statistically significant differences in contouring were found in 18% of the inter-center comparison. Less than a half of the centers could claim to have a good agreement between the internal ROs. CONCLUSIONS: The overall intra-institute and inter-institute agreement was moderate. Central lymph-node levels were the most critical and variability increased as the complexity of the patient's anatomy increased. These findings might have an effect on the interpretation of results from multicenter and even mono-institute studies.

Atlas-based segmentation in breast cancer radiotherapy: Evaluation of specific and generic-purpose atlases.

OBJECTIVES: Atlas-based automatic segmentation (ABAS) addresses the challenges of accuracy and reliability in manual segmentation. We aim to evaluate the contribution of specific-purpose in ABAS of breast cancer (BC) patients with respect to generic-purpose libraries. MATERIALS AND METHODS: One generic-purpose and 9 specific-purpose libraries, stratified according to type of surgery and size of thorax circumference, were obtained from the computed tomography of 200 BC patients. Keywords about contralateral breast volume and presence of breast expander/prostheses were recorded. ABAS was validated on 47 independent patients, considering manual segmentation from scratch as reference. Five ABAS datasets were obtained, testing single-ABAS and multi-ABAS with simultaneous truth and performance level estimation (STAPLE). Center of mass distance (CMD), average Hausdorff distance (AHD) and Dice similarity coefficient (DSC) between corresponding ABAS and manual structures were evaluated and statistically significant differences between different surgeries, structures and ABAS strategies were investigated. RESULTS: Statistically significant differences between patients who underwent different surgery were found, with superior results for conservative-surgery group, and between different structures were observed: ABAS of heart, lungs, kidneys and liver was satisfactory (median values: CMD<2 mm, DSC≥0.80, AHD<1.5 mm), whereas chest wall, breast and spinal cord obtained moderate performance (median values: 2 mm ≤ CMD<5 mm, 0.60 ≤ DSC<0.80, 1.5 mm ≤ AHD<4 mm) and esophagus, stomach, brachial plexus and supraclavicular nodes obtained poor performance (median CMD≥5 mm, DSC<0.60, AHD≥4 mm). The application of STAPLE algorithm generally yields higher performance and the use of keywords improves results for breast ABAS. CONCLUSION: The homogeneity in the selection of atlases based on multiple anatomical and clinical features and the use of specific-purpose libraries can improve ABAS performance with respect to generic-purpose libraries.