Implementation of a Commercial Deep Learning-Based Auto Segmentation Software in Radiotherapy: Evaluation of Effectiveness and Impact on Workflow.

Proper delineation of both target volumes and organs at risk is a crucial step in the radiation therapy workflow. This process is normally carried out manually by medical doctors, hence demanding timewise. To improve efficiency, auto-contouring methods have been proposed. We assessed a specific commercial software to investigate its impact on the radiotherapy workflow on four specific disease sites: head and neck, prostate, breast, and rectum. For the present study, we used a commercial deep learning-based auto-segmentation software, namely Limbus Contour (LC), Version 1.5.0 (Limbus AI Inc., Regina, SK, Canada). The software uses deep convolutional neural network models based on a U-net architecture, specific for each structure. Manual and automatic segmentation were compared on disease-specific organs at risk. Contouring time, geometrical performance (volume variation, Dice Similarity Coefficient-DSC, and center of mass shift), and dosimetric impact (DVH differences) were evaluated. With respect to time savings, the maximum advantage was seen in the setting of head and neck cancer with a 65%-time reduction. The average DSC was 0.72. The best agreement was found for lungs. Good results were highlighted for bladder, heart, and femoral heads. The most relevant dosimetric difference was in the rectal cancer case, where the mean volume covered by the 45 Gy isodose was 10.4 cm3 for manual contouring and 289.4 cm3 for automatic segmentation. Automatic contouring was able to significantly reduce the time required in the procedure, simplifying the workflow, and reducing interobserver variability. Its implementation was able to improve the radiation therapy workflow in our department.

Delta4 Discover transmission detector: A comprehensive characterization for in-vivo VMAT monitoring.

OBJECTIVE: To investigate the dosimetric behaviour, influence on photon beam fluence and error detection capability of Delta4 Discover transmission detector. METHODS: The transmission detector (TRD) was characterized on a TrueBeam linear accelerator with 6 MV beams. Linearity, reproducibility and dose rate dependence were investigated. The effect on photon beam fluence was evaluated in terms of beam profiles, percentage depth dose, transmission factor and surface dose for different open field sizes. The transmission factor of the 10x10 cm2 field was entered in the TPS's configuration and its correct use in the dose calculation was verified recalculating 17 clinical IMRT/VMAT plans. Surface dose was measured for 20 IMRT fields. The capability to detect different delivery errors was investigated evaluating dose gamma index, MLC gamma index and leaf position of 15 manually modified VMAT plans. RESULTS: TRD showed a linear dependence on MU. No dose rate dependence was observed. Short-term and long-term reproducibility were within 0.1% and 0.5%. The presence of the TRD did not significantly affect PDDs and profiles. The transmission factor of the 10x10 cm2 field size was 0.985 and 0.983, for FF and FFF beams respectively. The 17 recalculated plans met our clinical gamma-index passing rate, confirming the correct use of the transmission factor by the TPS. The surface dose differences for the open fields increase for shorter SSDs and greater field size. Differences in surface dose for the IMRT beams were less than 2%. Output variation ≥2%, collimator angle variations within 0.3°, gantry angle errors of 1°, jaw tracking and leaf position errors were detected. CONCLUSIONS: Delta4 Discover shows good linearity and reproducibility, is not dependent on dose rate and does not affect beam quality and dose profiles. It is also capable to detect dosimetric and geometric errors and therefore it is suitable for monitoring VMAT delivery.

Delineation of the larynx as organ at risk in radiotherapy: a contouring course within "Rete Oncologica Piemonte-Valle d'Aosta" network to reduce inter- and intraobserver variability.

AIMS: To evaluate the usefulness of a contouring course in reducing inter- and intraobserver variability in the definition of the larynx as organ at risk (OAR). METHODS: Within the "Rete Oncologica Piemonte-Valle d'Aosta" network, a contouring course focusing on larynx delineation was proposed. Twenty-six radiotherapist technicians (RTTs) experienced in delineating OARs were asked to contour larynx before and after the training. An expert radiation oncologist defined the reference volume for educational purpose. The contoured volumes obtained before and after the course were compared using descriptive statistics (mean value, standard deviation-SD, and coefficient of variation-COV) of volumes and maximum diameters. Conformity index (CI), dice coefficient (DC), and percentage of overlap were used to evaluate the spatial accuracy of the different volumes compared to the reference. Further analysis regarding the variation in the centre of mass (COM) displacement was performed. RESULTS: The mean volume was 40.4 cm3 before and 65.9 cm3 after the course, approaching the reference value. Mean anteroposterior, laterolateral, and craniocaudal diameters improved, getting each closer to the reference. Moreover, the COM moved approaching reference coordinates. Mean percentage of intersection and DC strongly increased after the course, rising from 57.76 to 93.83 % and from 0.68 to 0.89, respectively. CI enhanced from 0.06 to 0.31. CONCLUSIONS: This study shows an improvement in larynx definition after the contouring course with lower interobserver variability and major consistency compared to the reference volume. Other specific educational activities may further increase the quality of radiation therapy contouring in this setting.

Image-guided Intensity-modulated Radiotherapy for Prostate Cancer Employing Hypofractionation and Simultaneous Integrated Boost: Results of a Consecutive Case Series with Focus on Erectile Function.

AIM: To report on clinical outcomes of prostate cancer patients treated with hypofractionated radiotherapy employing a simultaneous integrated boost strategy. PATIENTS AND METHODS: A consecutive series of 104 patients affected with prostate cancer was treated with intensity-modulated radiotherapy using a hypofractionated schedule and a simultaneous integrated boost consisting of 70 Gy (2.5 Gy daily) to the prostate gland, 63 Gy to the seminal vesicles (2.25 Gy daily) and 53.2 Gy to the pelvic nodes (1.9 Gy daily) when needed, delivered in 28 fractions. All patients underwent image-guided radiotherapy procedure consisting of daily cone-beam computed tomography. RESULTS: After a median observation time of 26 (range=15-48) months, the 3-year biochemical failure-free survival was 96.5% [95% confidence interval (CI)=89%-98%], 3-year cancer-specific survival was 98.5% (95% CI=91%-99%) and 3-year overall survival was 96.5% (95% CI=89%-98%). The gastrointestinal and genitourinary toxicity profiles were mild with fewer than 2% of grade 3 events. Erectile function was partially affected by radiation in men potent at baseline. CONCLUSION: Hypofractionation delivered with intensity-modulated radiotherapy and a simultaneous integrated boost approach proved to be a safe and effective treatment option for patients with prostate cancer. Patients with a preserved baseline erectile function experience a decrease in functionality correlated with the mean dose received by penile bulb.

Relationships between bladder dose-volume/surface histograms and acute urinary toxicity after radiotherapy for prostate cancer.

BACKGROUND AND PURPOSE: DUE01 is an observational study aimed at developing predictive models of genito-urinary toxicity of patients treated for prostate cancer with conventional (1.8-2Gy/fr, CONV) or moderate hypo-fractionation (2.35-2.7Gy/fr, HYPO). The current analysis focused on the relationship between bladder DVH/DSH and the risk of International Prostate Symptoms Score (IPSS)⩾15/20 at the end of radiotherapy. MATERIALS AND METHODS: Planning and relevant clinical parameters were prospectively collected, including DVH/DSH, LQ-corrected (DVHc/DSHc) and weekly (DVHw/DSHw) histograms. Best parameters were selected by the differences between patients with/without IPSS⩾15/20 at the end of radiotherapy. Logistic uni- and backward multi-variable (MVA) analyses were performed. RESULTS: Data of 247 patients were available (CONV: 116, HYPO: 131). Absolute DVHw/DSHw and DVHc/DSHc predicted the risk of IPSS⩾15 at the end of radiotherapy (n=77/247); an MVA model including baseline IPSS, anti-hypertensive, T stage, the absolute surface receiving ⩾8.5Gy/week and ⩾12.5Gy/week was developed (AUC=0.78, 95% CI: 0.72-0.83). Similar AUC values were found if replacing DSHw with DVHw/DVHc/DSHc parameters. The impact of dose-volume/surface parameters remained when excluding patients with baseline IPSS⩾15 and in HYPO. IPSS⩾20 at the end of radiotherapy (n=27/247) was mainly correlated to baseline IPSS and T stage. CONCLUSIONS: Although the baseline IPSS was the main predictor, constraining v8.5w<56cc and v12.5w<5cc may significantly reduce acute GU toxicity.

Long term rectal function after high-dose prostatecancer radiotherapy: results from a prospective cohort study.

PURPOSE: To prospectively evaluate long-term late rectal bleeding (lrb) and faecal incontinence (linc) after high-dose radiotherapy (RT) for prostate cancer in the AIROPROS 0102 population, and to assess clinical/dosimetric risk factors. MATERIALS AND METHODS: Questionnaires of 515 patients with G0 baseline incontinence and bleeding scores (follow-up ≥6 years) were analysed. Correlations between lrb/linc and many clinical and dosimetric parameters were investigated by univariate and multivariate logistic analyses. The correlation between lrb/linc and symptoms during the first 3 years after RT was also investigated. RESULTS: Of 515 patients lrb G1, G2 and G3 was found in 32 (6.1%), 2 (0.4%) and 3 (0.6%) patients while linc G1, G2 and G3 was detected in 50 (9.7%), 3 (0.6%) and 3 (0.6%), respectively. The prevalence of G2-G3 lrb events was significantly reduced compared to the first 3-years (1% vs 2.7%, p=0.016) ≥G1 lrb was significantly associated with V75 Gy (OR=1.07). In multivariate analysis, ≥G1 linc was associated with V40 Gy (OR=1.015), use of antihypertensive medication (OR=0.38), abdominal surgery before RT (OR=4.7), haemorrhoids (OR=2.6), and G2-G3 acute faecal incontinence (OR=4.4), a nomogram to predict the risk of long-term ≥G1 linc was proposed. Importantly, the prevalence of ≥G1 linc was significantly correlated with the mean incontinence score during the first 3 years after RT (OR=16.3). CONCLUSIONS: Long-term (median: 7 years) rectal symptoms are prevalently mild and strongly correlated with moderate/severe events occurring in the first 3 years after RT. Linc was associated with several risk factors.

Five-year results of a prospective case series of accelerated hypofractionated whole breast radiation with concomitant boost to the surgical bed after conserving surgery for early breast cancer.

Accelerated hypofractionation (HF) using larger dose per fraction, delivered in fewer fractions over a shorter overall treatment time, is presently a consistent possibility for adjuvant whole breast radiation (WBRT) after breast-conserving surgery for early breast cancer (EBC). Between 2005 and 2008, we submitted 375 consecutive patients to accelerated hypofractionated WBRT after breast-conserving surgery for EBC. The basic course of radiation consisted of 45 Gy in 20 fractions over 4 weeks to the whole breast (2.25 Gy daily) with an additional daily concomitant boost of 0.25 Gy up to 50 Gy to the surgical bed. Overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS) and local control (LC) were assessed. Late toxicity was scored according to the CTCAE v3.0; acute toxicity using the RTOG/EORTC toxicity scale. Cosmesis was assessed comparing treated and untreated breast. Quality of life (QoL) was determined using EORTC QLQ-C30/QLQ-BR23 questionnaires. With a median follow-up of 60 months (range 42-88), 5 years OS, CSS, DFS and LC were 97.6, 99.4, 96.6 and 100 %, respectively. Late skin and subcutaneous toxicity was generally mild, with few events > grade 2 observed. Cosmetic results were excellent in 75.7 % of patients, good in 20 % and fair in 4.3 %. QoL, assessed both through QLQ-C30/QLQ-BR23, was generally favorable, within the functioning and symptoms domains. Our study is another proof of principle that HF WBRT with a concurrent boost dose to the surgical cavity represents a safe and effective postoperative treatment modality with excellent local control and survival, consistent cosmetic results and mild toxicity.

Does TomoDirect 3DCRT represent a suitable option for post-operative whole breast irradiation? A hypothesis-generating pilot study.

BACKGROUND: This study investigates the use of TomoDirect™ 3DCRT for whole breast adjuvant radiotherapy (AWBRT) that represents a very attractive treatment opportunity, mainly for radiotherapy departments without conventional Linacs and only equipped with helical tomotherapy units. METHODS: Plans were created for 17 breast cancer patients using TomoDirect in 3DCRT and IMRT modality and field-in-field 3DCRT planning (FIF) and compared in terms of PTV coverage, overdosage, homogeneity, conformality and dose to OARs. The possibility to define patient-class solutions for TD-3DCRT employment was investigated, correlating OARs dose constraints to patient specific anatomic parameters. RESULTS: TD-3DCRT showed PTV coverage and homogeneity significantly higher than TD-IMRT and FIF. PTV conformality was significantly better for FIF, while no differences were found between TD-3DCRT and TD-IMRT. TD-3DCRT showed mean values of the OARs dosimetric endpoints significantly higher than TD-IMRT; with respect to FIF, TD-3DCRT showed values significantly higher for lung V(20Gy), mean heart dose and V(25Gy), while contralateral lung maximum dose and contralateral breast mean dose resulted significantly lower. The Central Lung Distance (CLD) and the maximal Heart Distance (HD) resulted as useful clinical tools to predict the opportunity to employ TD-3DCRT: positive correlations were found between CLD and both V(20Gy) and mean lung dose and between HD and both V25Gy and the mean heart dose. TD-3DCRT showed a significantly shorter mean beam-on time than TD-IMRT. CONCLUSIONS: The present study showed that TD-3DCRT and TD-IMRT are two feasible and dosimetrically acceptable treatment approach for AWBRT, with an optimal PTV coverage and adequate OARs sparing. Some concerns might be raised in terms of dose to organs at risks if TD-3DCRT is applied to a general population. A correct patients clusterization according to simple quantitative anatomic measures, would help to correctly allocate patients to the appropriate treatment planning strategy in terms of target coverage, but also of normal tissue sparing.

Different IMRT solutions vs. 3D-conformal radiotherapy in early stage Hodgkin's Lymphoma: dosimetric comparison and clinical considerations.

BACKGROUND: Radiotherapy in Hodgkin's Lymphoma (HL) is currently evolving with new attempts to further reduce radiation volumes to the involved-node concept (Involved Nodes Radiation Therapy, INRT) and with the use of intensity modulated radiotherapy (IMRT). Currently, IMRT can be planned and delivered with several techniques, and its role is not completely clear. We designed a planning study on a typical dataset drawn from clinical routine with the aim of comparing different IMRT solutions in terms of plan quality and treatment delivery efficiency. METHODS: A total of 10 young female patients affected with early stage mediastinal HL and treated with 30 Gy INRT after ABVD-based chemotherapy were selected from our database. Five different treatment techniques were compared: 3D-CRT, VMAT (single arc), B-VMAT ("butterfly", multiple arcs), Helical Tomotherapy (HT) and Tomodirect (TD). Beam energy was 6 MV, and all IMRT planning solutions were optimized by inverse planning with specific dose-volume constraints on OAR (breasts, lungs, thyroid gland, coronary ostia, heart). Dose-Volume Histograms (DVHs) and Conformity Number (CN) were calculated and then compared, both for target and OAR by a statistical analysis (Wilcoxon's Test). RESULTS: PTV coverage was reached for all plans (V95% ≥ 95%); highest mean CN were obtained with HT (0.77) and VMAT (0.76). B-VMAT showed intermediate CN mean values (0.67), while the lowest CN were obtained with TD (0.30) and 3D-CRT techniques (0.30). A trend of inverse correlation between higher CN and larger healthy tissues volumes receiving low radiation doses was shown for lungs and breasts. For thyroid gland and heart/coronary ostia, HT, VMAT and B-VMAT techniques allowed a better sparing in terms of both Dmean and volumes receiving intermediate-high doses compared to 3D-CRT and TD. CONCLUSIONS: IMRT techniques showed superior target coverage and OAR sparing, with, as an expected consequence, larger volumes of healthy tissues (lungs, breasts) receiving low doses. Among the different IMRT techniques, HT and VMAT showed higher levels of conformation; B-VMAT and HT emerged as the planning solutions able to achieve the most balanced compromise between higher conformation around the target and smaller volumes of OAR exposed to lower doses (typical of 3D-CRT).

Head and neck region consolidation radiotherapy and prophylactic cranial irradiation with hippocampal avoidance delivered with helical tomotherapy after induction chemotherapy for non-sinonasal neuroendocrine carcinoma of the upper airways.

BACKGROUND: Non-sinonasal neuroendocrine carcinomas (NSNECs) of the head and neck are considered an unfrequent clinico-pathological entity. Combined modality treatment represents an established therapeutic option for undifferentiated forms where distant metastasis is a common pattern of failure. METHODS: We report on a case of NSNEC treated with sequential chemo-radiation consisting of 6 cycles of cisplatin and etoposide followed by loco-regional radiation to the head and neck and simultaneous prophylactic cranial irradiation to prevent from intracranial spread, delivered with helical tomotherapy with the 'hippocampal avoidance' technique in order to reduce neuro-cognitive late effects. RESULTS: One year after the end of the whole combined modality approach, the patient achieved complete remission, with no treatment-related sub-acute and late effects. CONCLUSIONS: The present report highlights the importance of multidisciplinary management for NSNECs of the head and neck, as the possibility to achieve substantial cure rates with mild side effects with modern radiotherapy techniques.

The use of a diode matrix in commissioning activities for electron energies > or = 9 MeV: a feasibility study.

The contribution of a commercially available diode matrix (MapCHECK, provided by Sun Nuclear, Melbourne, FL) for the commissioning procedures of the voxel based Monte Carlo (VMC++) algorithm for electron beams of MasterPlan treatment planning system was investigated. The attention is mainly focused on the calculation in homogeneous and heterogeneous phantoms. With this aim, following a data set similar to that proposed by Electron Collaborative Working Group (ECWG), the dose profiles and two-dimensional (2D) dose distributions measured by the diode matrix were compared with the calculated ones using the gamma analysis method with acceptance criteria for the dose difference and the distance to agreement equal to 4% and 4 mm, respectively. The average and standard deviation of the percentage of points satisfying the constraint gamma < or = 1 are 98.3 +/- 4.1% and 99.3 +/- 1.7% for the 9 and 12 MeV electron beam, respectively, showing that the accuracy of MasterPlan electron beam algorithm is good for simple two-dimensional geometries as well as for more complicated three-dimensional ones. The results are in agreement with those reported in literature by Cygler et al. ["Evaluation of the first commercial Monte Carlo dose calculation engine for electron beam treatment planning," Med. Phys. 31, 142-153 (2004)]. In addition, the authors have also analyzed the response of the 2D array in terms of dose profiles at different depths, comparing the results with those obtained in water phantom using an electron diode. The results show that in the low gradient regions there were no deviations larger than the criteria of acceptability set by Van Dyk et al. ["Commissioning and quality assurance of treatment planning computers," Int. J. Radiat. Oncol. Biol. Phys. 26, 261-273 (1993)]; in the high gradient region, the maximum deviations are less than 2 mm with most of the values less than 1 mm. The present article shows that MapCHECK can play a useful role in the commissioning of electron algorithms of treatment planning systems in the evaluation of the 2D dose distributions in homogeneous and heterogeneous phantoms. In fact, it provides accurate results with the merit of expediting the commissioning process by using measuring device that requires minimal setup time and data processing time.

Verification of Varian Enhanced Dynamic Wedge implementation in masterplan treatment planning system.

This paper investigates the accuracy of the two available calculation algorithms of the Oncentra MasterPlan three-dimensional treatment planning system (TPS)-- the pencil beam method and collapsed-cone convolution--in modeling the Varian enhanced dynamic wedge (EDW). Measurements were carried out for a dual high energy (6-15 MV) Varian DHX-S linear accelerator using ionization chambers for beam axis measurements (wedge factors and depth doses), film dosimetry for off-axis dose profiles measurements, and a diode matrix detector for two dimensional absolute dose distributions. Using both calculation algorithms, different configuration of symmetric and asymmetric fields varying the wedge's angle were tested. Accuracy of the treatment planning system was evaluated in terms of percentage differences between measured and calculated values for wedge factors, depth doses, and profiles. As far as the absolute dose distribution was concerned, the gamma index method (Low et al.) was used with 3% and 3 mm as acceptance criteria for dose difference and distance-to-agreement, respectively. Wedge factors and percentage depth doses were within 1% deviation between calculated and measured values. The comparison of measured and calculated dose profiles shows that the Van Dyk's acceptance criteria (Van Dyk et al.) are generally met; a disagreement can be noted for large wedge angles and field size limited to the low dose-low gradient region only. The 2D absolute dose distribution analysis confirms the good accuracy of the two calculation algorithms in modeling the enhanced dynamic wedge.

Clinical and dosimetric predictors of late rectal syndrome after 3D-CRT for localized prostate cancer: preliminary results of a multicenter prospective study.

PURPOSE: To assess the predictors of late rectal toxicity in a prospectively investigated group of patients treated at 70-80 Gy for prostate cancer (1.8-2 Gy fractions) with three-dimensional conformal radiotherapy. METHODS AND MATERIALS: A total of 1,132 patients were entered into the study between 2002 and 2004. Three types of rectal toxicity, evaluated by a self-administered questionnaire, mainly based on the subjective objective management, analytic late effects of normal tissue system, were considered: stool frequency/tenesmus/pain, fecal incontinence, and bleeding. The data from 506 patients with a follow-up of 24 months were analyzed. The correlation between a number of clinical and dosimetric parameters and Grade 2 or greater toxicity was investigated by univariate and multivariate (MVA) logistic analyses. RESULTS: Of the 1,132 patients, 21, 15, and 30 developed stool frequency/tenesmus/pain, fecal incontinence, and bleeding, respectively. Stool frequency/tenesmus/pain correlated with previous abdominal/pelvic surgery (MVA, p=0.05, odds ratio [OR], 3.3). With regard to incontinence, MVA showed the volume receiving>or=40 Gy (V40) (p=0.035, OR, 1.037) and surgery (p=0.02, OR, 4.4) to be the strongest predictors. V40 to V70 were highly predictive of bleeding; V70 showed the strongest impact on MVA (p=0.03), together with surgery (p=0.06, OR, 2.5), which was also the main predictor of Grade 3 bleeding (p=0.02, OR, 4.2). CONCLUSIONS: The predictive value of the dose-volume histogram was confirmed for bleeding, consistent with previously suggested constraints (V50<55%, V60<40%, V70<25%, and V75<5%). A dose-volume histogram constraint for incontinence can be suggested (V40<65-70%). Previous abdominal/pelvic surgery correlated with all toxicity types; thus, a modified constraint for bleeding (V70<15%) can be suggested for patients with a history of abdominal/pelvis surgery, although further validation on a larger population with longer follow-up is needed.

Transmission, penumbra and leaf positional accuracy in commissioning and quality assurance program of a multileaf collimator for step-and-shoot IMRT treatments.

AIMS AND BACKGROUND: The performance characteristics of a commercial multileaf collimator (MLC) for intensity modulated radiation therapy (IMRT) and a comprehensive quality assurance program (QA) to be performed during the commissioning of the MLC were investigated. MATERIALS AND METHODS: The midleaf transmission and interleaf leakage, the in-plane penumbra and its in-plane/cross-plane variation, the cross-plane penumbra and its in-plane/cross-plane variation, and the leaf positional accuracy of a high-energy photon (6 MV) Sli Precise Elekta linear accelerator were measured. Kodak EDR2 Ready Pack film was used for MLC transmission measurement; for the other characterization measurements we used Kodak X-Omat XV2 Ready Pack film placed at 5 cm depth in a solid RW3 phantom. Each film was digitized with a laser scanning photodensitometer VXR-12 Plus using the Omni Pro-Accept 6.OA film dosimetry system and converted to dose by means of H&D curves. The dose calibration measurements were performed with a Farmer ionization chamber according to the guidelines of the IAEA Technical Report No. 277. RESULTS: The average midleaf transmission and interleaf leakage were 1.8% +/- 0.1% and 2.1% +/- 0.2%, respectively. The average value of the cross-plane penumbra was 5.4 mm +/- 0.3 mm with maximum variation less than 0.4 mm and 1.0 mm in the in-plane and cross-plane direction, respectively. The average value of the in-plane penumbra was 3.2 mm +/- 0.2 mm and 3.5 mm +/- 0.2 mm for the step side and groove side of the leaves, respectively. A dose profile perpendicular to the direction of the leaf travel passing through the central axis shows a tongue-and-groove effect of about 33%. The positional accuracy of the leaves was investigated according to AAPM Report No. 72 TG50; the deviation of the net optical density along all the match lines was less than +/- 20%. Moreover, the results obtained with a step field technique showed a positional accuracy of less than 1 mm. CONCLUSIONS: The results suggest the necessity of extensive knowledge of the MLC dosimetric characteristics for IMRT applications in order to allow physicists to study their influence on treatment delivery and to perform a comprehensive routine QA program of the investigated parameters.