Anatomical changes and dosimetric analysis of the neck region based on FBCT for nasopharyngeal carcinoma patients during radiotherapy.

BACKGROUND: The study aimed to investigate anatomical changes in the neck region and evaluate their impact on dose distribution in patients with nasopharyngeal carcinoma (NPC) undergoing intensity modulated radiation therapy (IMRT). Additionally, the study sought to determine the optimal time for replanning during the course of treatment. METHODS: Twenty patients diagnosed with NPC underwent IMRT, with weekly pretreatment kV fan beam computed tomography (FBCT) scans in the treatment room. Metastasized lymph nodes in the neck region and organs at risk (OARs) were redelineation using the images from the FBCT scans. Subsequently, the original treatment plan (PLAN0) was replicated to each FBCT scan to generate new plans labeled as PLAN 1-6. The dose-volume histograms (DVH) of the new plans and the original plan were compared. One-way repeated measure ANOVA was utilized to establish threshold(s) at various time points. The presence of such threshold(s) would signify significant change(s), suggesting the need for replanning. RESULTS: Progressive volume reductions were observed over time in the neck region, the gross target volume for metastatic lymph nodes (GTVnd), as well as the submandibular glands and parotids. Compared to PLAN0, the mean dose (Dmean) of GTVnd-L significantly increased in PLAN5, while the minimum dose covering 95% of the volume (D95%) of PGTVnd-L showed a significant decrease from PLAN3 to PLAN6. Similarly, the Dmean of GTVnd-R significantly increased from PLAN4 to PLAN6, whereas the D95% of PGTVnd-R exhibited a significant decrease during the same period. Furthermore, the dose of bilateral parotid glands, bilateral submandibular glands, brainstem and spinal cord was gradually increased in the middle and late period of treatment. CONCLUSION: Significant anatomical and dosimetric changes were noted in both the target volumes and OARs. Considering the thresholds identified, it is imperative to undertake replanning at approximately 20 fractions. This measure ensures the delivery of adequate doses to target volumes while mitigating the risk of overdosing on OARs.

Extensive clinical testing of Deep Learning Segmentation models for thorax and breast cancer radiotherapy planning.

BACKGROUND: The performance of deep learning segmentation (DLS) models for automatic organ extraction from CT images in the thorax and breast regions was investigated. Furthermore, the readiness and feasibility of integrating DLS into clinical practice were addressed by measuring the potential time savings and dosimetric impact. MATERIAL AND METHODS: Thirty patients referred to radiotherapy for breast cancer were prospectively included. A total of 23 clinically relevant left- and right-sided organs were contoured manually on CT images according to ESTRO guidelines. Next, auto-segmentation was executed, and the geometric agreement between the auto-segmented and manually contoured organs was qualitatively assessed applying a scale in the range [0-not acceptable, 3-no corrections]. A quantitative validation was carried out by calculating Dice coefficients (DSC) and the 95% percentile of Hausdorff distances (HD95). The dosimetric impact of optimizing the treatment plans on the uncorrected DLS contours, was investigated from a dose coverage analysis using DVH values of the manually delineated contours as references. RESULTS: The qualitative analysis showed that 93% of the DLS generated OAR contours did not need corrections, except for the heart where 67% of the contours needed corrections. The majority of DLS generated CTVs needed corrections, whereas a minority were deemed not acceptable. Still, using the DLS-model for CTV and heart delineation is on average 14 minutes faster. An average DSC=0.91 and H95=9.8 mm were found for the left and right breasts, respectively. Likewise, and average DSC in the range [0.66, 0.76]mm and HD95 in the range [7.04, 12.05]mm were found for the lymph nodes. CONCLUSION: The validation showed that the DLS generated OAR contours can be used clinically. Corrections were required to most of the DLS generated CTVs, and therefore warrants more attention before possibly implementing the DLS models clinically.

Intra-therapeutic dosimetry of [177Lu]Lu-PSMA-617 in low-volume hormone-sensitive metastatic prostate cancer patients and correlation with treatment outcome.

INTRODUCTION: While [177Lu]Lu-PSMA radioligand therapy is currently only applied in end-stage metastatic castrate-resistant prostate cancer (mCRPC) patients, also low-volume hormone-sensitive metastatic prostate cancer (mHSPC) patients can benefit from it. However, there are toxicity concerns related to the sink effect in low-volume disease. This prospective study aims to determine the kinetics of [177Lu]Lu-PSMA in mHSPC patients, analyzing the doses to organs at risk (salivary glands, kidneys, liver, and bone marrow) and tumor lesions < 1 cm diameter. METHODS: Ten mHSPC patients underwent two cycles of [177Lu]Lu-PSMA therapy. Three-bed position SPECT/CT was performed at 5 time points after each therapy. Organ dosimetry and lesion dosimetry were performed using commercial software and a manual approach, respectively. Correlation between absorbed index lesion dose and treatment response (PSA drop of > 50% at the end of the study) was calculated and given as Spearman's r and p-values. RESULTS: Kinetics of [177Lu]Lu-PSMA in mHSPC patients are comparable to those in mCRPC patients. Lesion absorbed dose was high (3.25 ± 3.19 Gy/GBq) compared to organ absorbed dose (salivary glands: 0.39 ± 0.17 Gy/GBq, kidneys: 0.49 ± 0.11 Gy/GBq, liver: 0.09 ± 0.01 Gy/GBq, bone marrow: 0.017 ± 0.008 Gy/GBq). A statistically significant correlation was found between treatment response and absorbed index lesion dose (p = 0.047). CONCLUSIONS: We successfully performed small lesion dosimetry and showed that the tumor sink effect in mHSPC patients is of less concern than was expected. Tumor-to-organ ratio of absorbed dose was high and tumor uptake correlates with PSA response. Additional treatment cycles are legitimate in terms of organ toxicity and could lead to better tumor response.

Baseline FDG PET/CT in free breathing versus deep inspiration breath-hold for pediatric patients with mediastinal lymphoma.

INTRODUCTION: The prospective TEDDI protocol investigates the feasibility of radiotherapy delivery in deep inspiration breath-hold (DIBH) for pediatric patients. To secure optimal radiotherapy planning, a diagnostic baseline FDG PET/CT in free breathing (FB) and DIBH was acquired. The anatomical changes in the mediastinum and the effect on PET metrics between the two breathing conditions were assessed for pediatric patients with mediastinal lymphoma. MATERIAL AND METHODS: Ten patients aged 5-17 were included and had a PET/CT in FB and DIBH. Metabolic active lymphoma volumes were manually delineated with a visually based segmentation method and the PET metrics were extracted. The anatomical lymphoma, lung and heart volumes were delineated on CT. RESULTS: The lung volume increased while the heart was displaced caudally and separated from the lymphoma in DIBH compared to FB. Both the anatomical and the metabolically active lymphoma volumes appeared different regarding shape and configuration in the two breathing conditions. The image quality of the DIBH PET was equal to the FB PET regarding interpretation and delineation of lymphoma lesions. All PET metrics increased on the DIBH PET compared to the FB PET with the highest increase observed for the maximum standardized uptake value (33%, range 7-56%). CONCLUSION: Diminished respiratory motion together with anatomical changes within the lymphoma increased all PET metrics in DIBH compared to FB. The anatomical changes observed in DIBH compared to FB are expected to reduce radiation doses to the heart and lungs in pediatric patients with mediastinal lymphoma referred for radiotherapy delivery in DIBH and, thereby, reduce their risk of late effects. TRIAL REGISTRATION: The Danish Ethical Committee (H-16035870, approved November 24th 2016), the Danish Data Protection Agency (2012-58-0004, approved 1 January 2017). Registered retrospectively at clinicaltrials.gov (NCT03315546, 20 October 2017).

Sparing the hippocampus and the hypothalamic- pituitary region during whole brain radiotherapy: a volumetric modulated arc therapy planning study.

BACKGROUND: Feasibility testing of a simultaneous sparing approach of hippocampus, hypothalamus and pituitary gland in patients undergoing whole-brain radiotherapy (WBRT) with and without a concomitant boost to metastatic sites. INTRODUCTION: Cognitive impairment and hormonal dysfunction are common side effects of cranial radiotherapy. A reduced dose application to the patho-physiologically involved functional brain areas, i.e. hippocampus, hypothalamus and pituitary gland, could reduce these common side effects. While hippocampal sparing is already a common practice to improve cognitive outcome, technical experience of additional combined sparing of the hypothalamus/pituitary gland (HT-P) is insufficient. METHODS: Twenty patients were included in the planning study. In 11 patients, a total dose of 36 Gy of WBRT (2 Gy per fraction) plus a simultaneous integrated boost (SIB) of 9 Gy (0.5 Gy per fraction, total dose: 45 Gy) to the brain metastases was applied. In 9 patients, prophylactic cranial irradiation (PCI) was simulated with a total dose of 30 Gy (2 Gy per fraction). In both patient cohorts, a sparing approach of the hippocampus and the HT-P area was simulated during WBRT. For all treatment plans, volumetric modulated arc therapy (VMAT) was used. Quality assurance included assessment of homogeneity, conformality and target coverage. RESULTS: The mean dose to the hippocampus and HT-P region was limited to less than 50% of the prescribed dose to the planning target volume (PTV) in all treatment plans. Dose homogeneity (HI) of the target volume was satisfying (median HI = 0.16 for WBRT+SIB and 0.1 for PCI) and target coverage (conformation number, CN) was not compromised (median CN = 0.82 for SIB and 0.86 for PCI). CONCLUSION: Simultaneous dose reduction to the hippocampus and the HT-P area did not compromise the PTV coverage in patients undergoing WBRT+SIB or PCI using VMAT. While the feasibility of the presented approach is promising, prospective neurologic, endocrine outcome and safety studies are required.

Whole-brain irradiation with hippocampal sparing and dose escalation on metastases: neurocognitive testing and biological imaging (HIPPORAD) - a phase II prospective randomized multicenter trial (NOA-14, ARO 2015-3, DKTK-ROG).

BACKGROUND: Whole brain radiation therapy (WBRT) is the standard therapy for multiple brain metastases. However, WBRT has a poor local tumor control and is associated with a decline in neurocognitive function (NCF). Aim of this trial is to assess the efficacy and safety of a new treatment method, the WBRT with hippocampus avoidance (HA) combined with the simultaneous integrated boost (SIB) on metastases/resection cavities (HA-WBRT+SIB). METHODS: This is a prospective, randomized, two-arm phase II multicenter trial comparing the impact of HA on NCF after HA-WBRT+SIB versus WBRT+SIB in patients with multiple brain metastases. The study design is double-blinded. One hundred thirty two patients are to be randomized with a 1:1 allocation ratio. Patients between 18 and 80 years old are recruited, with at least 4 brain metastases of solid tumors and at least one, but not exceeding 10 metastases ≥5 mm. Patients must be in good physical condition and have no metastases/resection cavities in or within 7 mm of the hippocampus. Patients with dementia, meningeal disease, cerebral lymphomas, germ cell tumors, or small cell carcinomas are excluded. Previous irradiation and resection of metastases, as well as the number and size of metastases to be boosted have to comply with certain restrictions. Patients are randomized between the two treatment arms: HA-WBRT+SIB and WBRT+SIB. WBRT is to be performed with 30 Gy in 12 daily fractions and the SIB with 51 Gy/42 Gy in 12 daily fractions on 95% of volume for metastases/resection cavities. In the experimental arm, the dose to the hippocampi is restricted to 9 Gy in 98% of the volume and 17Gy in 2% of the volume. NCF testing is scheduled before WBRT, after 3 (primary endpoint), 9, 18 months and yearly thereafter. Clinical and imaging follow-ups are performed 6 and 12 weeks after WBRT, after 3, 9, 18 months and yearly thereafter. DISCUSSION: This is a protocol of a randomized phase II trial designed to test a new strategy of WBRT for preventing cognitive decline and increasing tumor control in patients with multiple brain metastases. TRIAL REGISTRATION: The HIPPORAD trial is registered with the German Clinical Trials Registry (DRKS00004598, registered 2 June 2016).

Target miss using PTV-based IMRT compared to robust optimization via coverage probability concept in prostate cancer.

Purpose: Cure- and toxicity rates of prostate IGRT can both be affected by ill-chosen planning target volume (PTV) margins. For dose-escalated prostate radiotherapy, we studied the potential for organ at risk (OAR) sparing and compensation of prostate motion with robust plan optimization using the coverage probability (CovP) concept compared to conventional PTV-based IMRT.Material and methods: We evaluated plan quality of CovP-plans for 27 intermediate risk prostate cancer patients treated in a prospective study (78 Gy/39 fractions). Clinical target volume (CTV) and OARs were contoured on three separate CTs to capture movement and deformation. To define the internal target volume (ITV), the union of CTV1-3 was encompassed by an isotropic margin of 7 mm for the planning process. CovP-dose distribution is optimized considering weight factors for IMRT constraints derived from probabilities of systematic organ displacement in the three CTs. CovP-dose volume histograms (DVHs) were compared with additionally calculated conventional PTV-based IMRT plans. PTV-based IMRT was planned on one-single CT with an isotropically expanded CTV to generate the PTV (i.e., CTV1 + 7mm) and was evaluated on the two other CTs.Results: The CovP-concept showed higher robustness in target volume coverage. Target miss was frequently observed with PTV-based IMRT, resulting in cold spots until 70 Gy with the CovP-concept. The target dose at 74 Gy was comparable, while further the dose-escalation (75-78 Gy) was improved with PTV-based IMRT. However, dose-escalation with PTV-based IMRT was associated with increased OAR-doses, especially in high-dose areas.Conclusions: Probabilistic dose-escalated IMRT was feasible in this prospective study. Comparison of the CovP-concept with PTV-based IMRT revealed superiority with regard to target-coverage and sparing of OARs. The CovP-concept implements a robust plan optimization strategy for organ deformation and motions and could, therefore, serve as a less demanding compromise on the way to adaptive IGRT avoiding daily time-consuming re-planning. SUMMARYWe evaluated the robustness of coverage probability (CovP)-based IMRT plans within a prospective study for prostate cancer radiotherapy. The treatment plans were compared with newly calculated conventional PTV-based IMRT plans. We were able to show that CovP led to a clearly more robust target coverage by avoiding hot spots at OARs compared to conventional PTV-based IMRT. In addition, negative consequences of an inflated PTV can be ameliorated by a more relaxed CovP-based dose prescription.

Automatic segmentation of pelvic organs-at-risk using a fusion network model based on limited training samples.

Background: Efficient and accurate methods are needed to automatically segmenting organs-at-risk (OAR) to accelerate the radiotherapy workflow and decrease the treatment wait time. We developed and evaluated the use of a fused model Dense V-Network for its ability to accurately segment pelvic OAR.Material and methods: We combined two network models, Dense Net and V-Net, to establish the Dense V-Network algorithm. For the training model, we adopted 100 kV computed tomography (CT) images of patients with cervical cancer, including 80 randomly selected as training sets, by which to adjust parameters of the automatic segmentation model, and the remaining 20 as test sets to evaluate the performance of the convolutional neural network model. Three representative parameters were used to evaluate the segmentation results quantitatively.Results: Clinical results revealed that Dice similarity coefficient values of the bladder, small intestine, rectum, femoral head and spinal cord were all above 0.87 mm; and Jaccard distance was within 2.3 mm. Except for the small intestine, the Hausdorff distance of other organs was less than 9.0 mm. Comparison of our approaches with those of the Atlas and other studies demonstrated that the Dense V-Network had more accurate and efficient performance and faster speed.Conclusions: The Dense V-Network algorithm can be used to automatically segment pelvic OARs accurately and efficiently, while shortening patients' waiting time and accelerating radiotherapy workflow.

Radiation dose-painting with protons vs. photons for head-and-neck cancer.

Background: Dose-painting has recently been investigated in early-phase trials in head-and-neck cancer (HNC) with the aim of improving local tumor control. At the same time proton therapy has been reported as potentially capable of decreasing toxicity. Here, we investigate whether protons could be applied in a dose-painting setting by comparing proton dose distributions with delivered photon plans from a phase-I trial of FDG-PET based dose-painting at our institution.Material and methods: Eleven oropharynx (5), hypopharynx (2) and larynx cancer (4) patients from the recently conducted phase I trial were used for comparison of proton and photon dose-painting techniques. Robust optimization (3.5%/3 mm) was used for proton plans. Plan robustness and difference in dose metrics to targets and organs at risk were evaluated.Results: The proton plans met target dose constraints, while having lower non-target dose than photon plans (body-minus-CTV, mean dose 3.9 Gy vs 7.2 Gy, p = .004). Despite the use of robust proton planning for plan max dose, photon plan max doses were more robust (p = .006). Max dose to medulla, brainstem and mandible were lower in the proton plans, while there was no significant difference in mean dose to submandibular- and parotid glands.Conclusion: Proton dose-painting for HNC seems feasible and can reduce the non-target dose overall, however not significantly to certain organs close to the target, such as the salivary glands. Max dose in proton plans had a lower robustness compared to photons, requiring caution to avoid unintended hot spots in consideration of the risk of mucosal toxicity.

Keep Your Landmarks Close and the Hypogastric Nerve Closer: An Approach to Nerve-sparing Endometriosis Surgery.

OBJECTIVE: Excisional techniques used to surgically treat deep infiltrating endometriosis (DIE) can result in inadvertent damage to the autonomic nervous system of the pelvis, leading to urinary, anorectal, and sexual dysfunction [1-4]. This educational video illustrates the autonomic neuroanatomy of the pelvis, identifying the predictable location of the hypogastric nerve in relation to other pelvic landmarks, and demonstrates a surgical technique for sparing the hypogastric nerve and inferior hypogastric plexus. DESIGN: Using didactic schematics and medical drawings, we discuss and illustrate the autonomic neuroanatomy of the pelvis. With annotated laparoscopic footage, we demonstrate a stepwise approach for identifying, dissecting, and preserving the hypogastric nerve during pelvic surgery. SETTING: Tertiary care academic hospitals: Mount Sinai Hospital in Toronto, Ontario, Canada, and S. Orsola Hospital in Bologna, Italy. INTERVENTIONS: Radical excision of DIE with adequate identification and sparing of the hypogastric nerve and inferior hypogastric plexus bilaterally was performed, following an overview of pelvic neuroanatomy. The superior hypogastric plexus was described and the hypogastric nerve, the most superficial and readily identifiable component of the inferior hypogastric plexus, was identified and used as a landmark to preserve autonomic bundles in the pelvis. The following steps, illustrated with laparoscopic footage, describe a surgical technique developed to identify and preserve the hypogastric nerve and the deeper inferior hypogastric plexus without the need for more extensive pelvic dissection to the level of the sacral nerve roots: (1) transperitoneal identification of the hypogastric nerve, with a pulling maneuver for confirmation; (2) opening of the retroperitoneum at the level of the pelvic brim and retroperitoneal identification of the ureter; (3) medial dissection and identification of the hypogastric nerve; and (4) lateralization of the hypogastric nerve, allowing for safe resection of DIE. CONCLUSION: The hypogastric nerve follows a predictable course and can be identified, dissected, and spared during pelvic surgery, making it an important landmark for the preservation of pelvic autonomic innervation.

Extended-field bone marrow sparing radiotherapy for primary chemoradiotherapy in cervical cancer patients with para-aortic lymphadenopathy: Volumetric-modulated arc therapy versus helical tomotherapy.

BACKGROUND: Extended-field (EF) bone marrow-sparing (BMS) radiotherapy is attracting interest for cervical cancer patients with para-aortic lymphadenopathy. OBJECTIVE: To compare dosimetric quality of volumetric-modulated arc therapy (VMAT) vs. helical tomotherapy (HT) during EF BMS radiotherapy. METHODS: HT dose-volume histogram parameters including (1) coverage, homogeneity, and conformity of target volumes, (2) sparing of organs-at-risk, (3) monitor units, and (4) estimated treatment time were compared with those of VMAT in 20 cervical cancer patients who underwent EF BMS radiotherapy. The pelvic and para-aortic regions received 45-Gy dose (25 fractions), with simultaneous integrated boost of 55 Gy (25 fractions) for pelvic and para-aortic lymphadenopathy, followed by a parametrial boost of 9 Gy (5 fractions). RESULTS: The HT-based and VMAT techniques achieved adequate and similar target volume coverage with good dose homogeneity and conformity, while sparing all organs-at-risk, including the rectum, bladder, bowel, bone marrow, femoral head, kidney, and spinal cord. The HT treatment plan had significantly higher monitor units (p < 0.001) and longer estimated treatment times (p < 0.001). CONCLUSIONS: VMAT and HT plans are suitable for EF BMS radiotherapy, which can achieve adequate target volume coverage while sufficiently sparing normal tissue. In addition, VMAT, compared to HT planning, yielded shorter estimated treatment times.

Dosimetric comparison of artificial walls of bladder and rectum with real walls in common prostate IMRT techniques: Patient and Monte Carlo study.

BACKGROUND: Rectum and bladder are hallow structures and considered as critical organs in prostate cancer intensity modulated radiotherapy (IMRT). Therefore, dose received by these organ walls must be considered for prediction of radiobiological effects. Contouring the real organ walls is quite difficult and time consuming in CT/MRI images, so the easy contouring artificial walls with uniform thickness could be appropriated alternatives. OBJECTIVE: To compare reconstructed artificial walls with real walls of bladder and rectum in common prostate IMRT techniques based on dose volume-histograms (DVHs) derived from artificial and real walls. METHODS: Artificial walls were reconstructed with 2-10 mm and 2-8 mm thicknesses for bladder and rectum, respectively. Four common IMRT techniques were applied to each patient. Spearman correlation was used to find the relation between the DVHs of true walls with artificial walls and whole organs. Monte Carlo (MC) simulations of the IMRT techniques and dosimetric comparison were also performed on a standard patient data. RESULTS: The 2 mm thickness artificial walls showed the minimum differences with the true bladder and rectum walls based on absolute evaluations (the maximum difference < 10cc and standard deviation < 15cc). However, relative evaluations showed that all the artificial walls had high correlations with real walls for selecting dose volume parameters. There was also good agreement between the treatment planning system and MC simulations results. CONCLUSION: The DVH of whole organs was not a good surrogate of the true wall. The 2 mm artificial walls can be regarded as good alternatives for both of rectum and bladder. However, in relative dose evaluations all studied artificial walls were appropriate.

Deep-learning-based detection and segmentation of organs at risk in nasopharyngeal carcinoma computed tomographic images for radiotherapy planning.

OBJECTIVE: Accurate detection and segmentation of organs at risks (OARs) in CT image is the key step for efficient planning of radiation therapy for nasopharyngeal carcinoma (NPC) treatment. We develop a fully automated deep-learning-based method (termed organs-at-risk detection and segmentation network (ODS net)) on CT images and investigate ODS net performance in automated detection and segmentation of OARs. METHODS: The ODS net consists of two convolutional neural networks (CNNs). The first CNN proposes organ bounding boxes along with their scores, and then a second CNN utilizes the proposed bounding boxes to predict segmentation masks for each organ. A total of 185 subjects were included in this study for statistical comparison. Sensitivity and specificity were performed to determine the performance of the detection and the Dice coefficient was used to quantitatively measure the overlap between automated segmentation results and manual segmentation. Paired samples t tests and analysis of variance were employed for statistical analysis. RESULTS: ODS net provides an accurate detection result with a sensitivity of 0.997 to 1 for most organs and a specificity of 0.983 to 0.999. Furthermore, segmentation results from ODS net correlated strongly with manual segmentation with a Dice coefficient of more than 0.85 in most organs. A significantly higher Dice coefficient for all organs together (p = 0.0003 < 0.01) was obtained in ODS net (0.861 ± 0.07) than in fully convolutional neural network (FCN) (0.8 ± 0.07). The Dice coefficients of each OAR did not differ significantly between different T-staging patients. CONCLUSION: The ODS net yielded accurate automated detection and segmentation of OARs in CT images and thereby may improve and facilitate radiotherapy planning for NPC. KEY POINTS: • A fully automated deep-learning method (ODS net) is developed to detect and segment OARs in clinical CT images. • This deep-learning-based framework produces reliable detection and segmentation results and thus can be useful in delineating OARs in NPC radiotherapy planning. • This deep-learning-based framework delineating a single image requires approximately 30 s, which is suitable for clinical workflows.

Automatic segmentation of cardiac substructures from noncontrast CT images: accurate enough for dosimetric analysis?

PURPOSE: We evaluated the feasibility of using an automatic segmentation tool to delineate cardiac substructures from noncontrast computed tomography (CT) images for cardiac dosimetry and toxicity analyses for patients with nonsmall cell lung cancer (NSCLC) after radiotherapy. MATERIAL AND METHODS: We used an in-house developed multi-atlas segmentation tool to delineate 11cardiac substructures, including the whole heart, four heart chambers, and six greater vessels, automatically from the averaged 4D-CT planning images of 49 patients with NSCLC. Two experienced radiation oncologists edited the auto-segmented contours. Times for automatic segmentation and modification were recorded. The modified contours were compared with the auto-segmented contours in terms of Dice similarity coefficient (DSC) and mean surface distance (MSD) to evaluate the extent of modification. Differences in dose-volume histogram (DVH) characteristics were also evaluated for the modified versus auto-segmented contours. RESULTS: The mean automatic segmentation time for all 11 structures was 7-9 min. For the 49 patients, the mean DSC values (±SD) ranged from .73 ± .08 to .95 ± .04, and the mean MSD values ranged from 1.3 ± .6 mm to 2.9 ± 5.1 mm. Overall, the modifications were small; the largest modifications were in the pulmonary vein and the inferior vena cava. The heart V30 (volume receiving dose ≥30 Gy) and the mean dose to the whole heart and the four heart chambers were not different for the modified versus the auto-segmented contours based on the statistically significant condition of p < .05. Also, the maximum dose to the great vessels was no different except for the pulmonary vein. CONCLUSIONS: Automatic segmentation of cardiac substructures did not require substantial modifications. Dosimetric evaluation showed no significant difference between the auto-segmented and modified contours for most structures, which suggests that the auto-segmented contours can be used to study cardiac dose-responses in clinical practice.

Intensity modulated proton therapy plan generation in under ten seconds.

Background: Treatment planning for intensity modulated proton therapy (IMPT) can be significantly improved by reducing the time for plan calculation, facilitating efficient sampling of the large solution space characteristic of IMPT treatments. Additionally, fast plan generation is a key for online adaptive treatments, where the adapted plan needs to be ideally available in a few seconds. However, plan generation is a computationally demanding task and, although dose restoration methods for adaptive therapy have been proposed, computation times remain problematic. Material and methods: IMPT plan generation times were reduced by the development of dedicated graphical processing unit (GPU) kernels for our in-house, clinically validated, dose and optimization algorithms. The kernels were implemented into a coherent system, which performed all steps required for a complete treatment plan generation. Results: Using a single GPU, our fast implementation was able to generate a complete new treatment plan in 5-10 sec for typical IMPT cases, and in under 25 sec for plans to very large volumes such as for cranio-spinal axis irradiations. Although these times did not include the manual input of optimization parameters or a final clinical dose calculation, they included all required computational steps, including reading of CT and beam data. In addition, no compromise was made on plan quality. Target coverage and homogeneity for four patient plans improved (by up to 6%) or remained the same (changes <1%). No worsening of dose-volume parameters of the relevant organs at risk by more than 0.5% was observed. Conclusions: Fast plan generation with a clinically validated dose calculation and optimizer is a promising approach for daily adaptive proton therapy, as well as for automated or highly interactive planning.

Comparison of the automatic segmentation of multiple organs at risk in CT images of lung cancer between deep convolutional neural network-based and atlas-based techniques.

BACKGROUND: In this study, a deep convolutional neural network (CNN)-based automatic segmentation technique was applied to multiple organs at risk (OARs) depicted in computed tomography (CT) images of lung cancer patients, and the results were compared with those generated through atlas-based automatic segmentation. MATERIALS AND METHODS: An encoder-decoder U-Net neural network was produced. The trained deep CNN performed the automatic segmentation of CT images for 36 cases of lung cancer. The Dice similarity coefficient (DSC), the mean surface distance (MSD) and the 95% Hausdorff distance (95% HD) were calculated, with manual segmentation results used as the standard, and were compared with the results obtained through atlas-based segmentation. RESULTS: For the heart, lungs and liver, both the deep CNN-based and atlas-based techniques performed satisfactorily (average values: 0.87 < DSC < 0.95, 1.8 mm < MSD < 3.8 mm, 7.9 mm < 95% HD <11 mm). For the spinal cord and the oesophagus, the two methods had statistically significant differences. For the atlas-based technique, the average values were 0.54 < DSC < 0.71, 2.6 mm < MSD < 3.1 mm and 9.4 mm < 95% HD <12 mm. For the deep CNN-based technique, the average values were 0.71 < DSC < 0.79, 1.2 mm < MSD <2.2 mm and 4.0 mm < 95% HD < 7.9 mm. CONCLUSION: Our results showed that automatic segmentation based on a deep convolutional neural network enabled us to complete automatic segmentation tasks rapidly. Deep convolutional neural networks can be satisfactorily adapted to segment OARs during radiation treatment planning for lung cancer patients.

Plan-library supported automated replanning for online-adaptive intensity-modulated proton therapy of cervical cancer.

Background: Intensity-modulated proton therapy is sensitive to inter-fraction variations, including density changes along the pencil-beam paths and variations in organ-shape and location. Large day-to-day variations are seen for cervical cancer patients. The purpose of this study was to develop and evaluate a novel method for online selection of a plan from a patient-specific library of prior plans for different anatomies, and adapt it for the daily anatomy. Material and methods: The patient-specific library of prior plans accounting for altered target geometries was generated using a pretreatment established target motion model. Each fraction, the best fitting prior plan was selected. This prior plan was adapted using (1) a restoration of spot-positions (Bragg peaks) by adapting the energies to the new water equivalent path lengths; and (2) a spot addition to fully cover the target of the day, followed by a fast optimization of the spot-weights with the reference point method (RPM) to obtain a Pareto-optimal plan for the daily anatomy. Spot addition and spot-weight optimization could be repeated iteratively. The patient cohort consisted of six patients with in total 23 repeat-CT scans, with a prescribed dose of 45 Gy(RBE) to the primary tumor and the nodal CTV. Using a 1-plan-library (one prior plan based on all motion in the motion model) was compared to choosing from a 2-plan-library (two prior plans based on part of the motion). Results: Applying the prior-plan adaptation method with one iteration of adding spots resulted in clinically acceptable target coverage ( V95%≥95% and V107%≤2% ) for 37/46 plans using the 1-plan-library and 41/46 plans for the 2-plan-library. When adding spots twice, the 2-plan-library approach could obtain acceptable coverage for all scans, while the 1-plan-library approach showed V107%>2% for 3/46 plans. Similar OAR results were obtained. Conclusion: The automated prior-plan adaptation method can successfully adapt for the large day-to-day variations observed in cervical cancer patients.

Daily adaptive proton therapy - the key to innovative planning approaches for paranasal cancer treatments.

Background: For proton therapy of paranasal tumors, field directions avoiding volumes that might change during therapy are typically used. If the plan is optimized on the daily anatomy using daily adapted proton therapy (DAPT) however, field directions crossing the nasal cavities might be feasible. In this study, we investigated the effectiveness of DAPT for enabling narrow-field treatment approaches. Material and methods: For five paranasal tumor patients, representing a wide patient spectrum, anatomically robust 4-field-star and narrow-field plans were calculated and their robustness to anatomical and setup uncertainties was compared with and without DAPT. Based on the nominal planning CTs, per patient up to 125 simulated CTs (simCTs) with different nasal cavity fillings were created and random translations and rotations due to patient setup uncertainties were further simulated. Plans were recalculated or re-optimized on all error scenarios, representing non-adapted and DAPT fractions, respectively. From these, 100 possible treatments (60 GyRBE, 30 fx) were simulated and changes in integral dose, target and organs at risk (OARs) doses evaluated. Results: In comparison to the 4-field-star approach, the use of narrow-fields reduced integral dose between 29% and 56%. If OARs did not overlap with the target, OAR doses were also reduced. Finally, the significantly reduced target coverage in non-adapted treatments (mean V95 reductions of up to 34%) could be almost fully restored with DAPT in all cases (differences <1%). Conclusions: DAPT was found to be not only an effective way to increase plan robustness to anatomical and positional uncertainties, but also opened the possibility to use improved and more conformal field arrangements.

Organ sparing potential and inter-fraction robustness of adaptive intensity modulated proton therapy for lung cancer.

Background: The aim of this study was to compare adaptive intensity modulated proton therapy (IMPT) robustness and organ sparing capabilities with that of adaptive volumetric arc photon therapy (VMAT).Material and methods: Eighteen lung cancer patients underwent a planning 4DCT (p4DCT) and 5 weekly repeated 4DCT (r4DCT) scans. Target volumes and organs at risk were manually delineated on the three-dimensional (3D) average scans of the p4DCT (av_p4DCT) and of the r4DCT scans (av_r4DCT). Planning target volume (PTV)-based VMAT plans and internal clinical target volume (ICTV)-based robust IMPT plans were optimized in 3D on the av_p4DCT and re-calculated on the av_r4DCTs. Re-planning on av_r4DCTs was performed when indicated and accumulated doses were evaluated on the av_p4DCT.Results: Adaptive VMAT and IMPT resulted in adequate ICTV coverage on av_r4DCT in all patients and adequate accumulated-dose ICTV coverage on av_p4DCT in 17/18 patients (due to a shrinking target in one patient). More frequent re-planning was needed for IMPT than for VMAT. The average mean heart dose reduction with IMPT compared with VMAT was 4.6 Gy (p = .001) and it was >5 Gy for five patients (6, 7, 8, 15, and 22 Gy). The average mean lung dose reduction was 3.2 Gy (p < .001). Significant reductions in heart and lung V5 Gy were observed with IMPT.Conclusion: Robust-planned IMPT required re-planning more often than VMAT but resulted in similar accumulated ICTV coverage. With IMPT, heart and lung mean dose values and low dose regions were significantly reduced. Substantial cardiac sparing was obtained in a subgroup of five patients (28%).

Radiation-induced brachial plexus toxicity after SBRT of apically located lung lesions.

Purpose: To evaluate the rate and dose response of brachial plexus toxicity post stereotactic body radiation therapy (SBRT) of apically situated lung lesions. Material/methods: We retrospectively identified all patients with apically located tumors, defined by the epicenter of the tumor being located superiorly to the aortic arch, and treated with SBRT between 2008 and 2013. Patients with a shorter follow-up than 6 months were excluded. Primary aim was to evaluate radiation-induced brachial plexopathy (RIBP). Dose to the plexus was assessed by a retrospective delineation of the brachial plexus on the CT used for treatment planning. Then, Dmax, D0.1cc, D1cc and D3.0cc of the brachial plexus were collected from the dose-volume histograms (DVH) and recalculated to the biologically effective dose (BED) using α/ß = 3 Gy. A normal tissue complication probability (NTCP) model, based on four different dose-volume parameters (BED3,max, BED3,0.1cc, BED3,1.0cc, BED3,3.0cc) was fitted to the data. Results: Fifty-two patients with 56 apically located tumors were identified. Median prescription dose per fraction was 15 Gy (range 6-17) and median number of fractions was 3 (3-10). With a median follow-up of 30 months (6.1-72) seven patients experienced maximum grade 2 (scored 3 times) or 3 (scored 4 times) RIBP after a median of 8.7 months (range 4.0-31). Three patients had combined symptoms with pain, sensory and motor affection and four patients had isolated pain. Median BED3,max for the patients experiencing RIBP was 381 Gy (range 30-524) versus BED3,max of 34 Gy (range 0.10-483) for the patients without RIBP. The NTCP models showed a very high predictive ability (area under the receiver operating characteristic curve (AUC) 0.80-0.88). Conclusion: SBRT of apically located lung lesions may cause severe neurological symptoms; for a three-fraction treatment, we suggest that the maximum dose to the plexus should be kept ≤30 Gy (130 Gy BED3).