Dosimetric Comparison and Evaluation of 4 Stereotactic Body Radiotherapy Techniques for the Treatment of Prostate Cancer

Purpose:The aim of this study was to compare dosimetric characteristics, monitor unit, and delivery efficiency of 4 different stereotactic body radiotherapy techniques for the treatment of prostate cancer.Methods:This study included 8 patients with localized prostate cancer. Dosimetric assets of 4 delivery techniques for stereotactic body radiotherapy were evaluated: robotic CyberKnife, noncoplanar intensity-modulated radiotherapy, and 2 intensity-modulated arc therapy techniques (RapidArc and Elekta volumetric-modulated arc therapy). All the plans had equal treatment margins and a prescription dose of 35 Gy in 5 fractions.Results:Statistically significant differences were observed in homogeneity index and mean doses of bladder wall and penile bulb, all of which were highest with CyberKnife. No significant differences were observed in the mean doses of rectum, with values of 15.2 2.6, 13.3 +/- 2.6, 13.1 +/- 2.8, and 13.8 +/- 1.6 Gy with CyberKnife, RapidArc, volumetric-modulated arc therapy, and noncoplanar intensity-modulated radiotherapy, respectively. The highest dose conformity was realized with RapidArc. The dose coverage of the planning target volume was lowest with noncoplanar intensity-modulated radiotherapy. Treatment times and number of monitor units were largest with CyberKnife (on average 34.0 +/- 5.0 minutes and 8704 +/- 1449 monitor units) and least with intensity-modulated arc therapy techniques (on average 5.1 +/- 1.1 minutes and 2270 +/- 497 monitor units).Conclusion:Compared to CyberKnife, the RapidArc, volumetric-modulated arc therapy, and noncoplanar intensity-modulated radiotherapy produced treatment plans with similar dosimetric quality, with RapidArc achieving the highest dose conformity. Overall, the dosimetric differences between the studied techniques were marginal, and thus, the choice of the technique should rather focus on the delivery accuracies and dose delivery times.Peer reviewe

Recurrence of head and neck squamous cell carcinoma in relation to high-risk treatment volume

Background: Locoregional recurrence remains a major cause of failure in head and neck squamous cell carcinoma (HNSCC). Human papilloma virus (HPV)-associated HNSCCs generally have a good prognosis but may recur even after standard photon radiotherapy (RT). Another incentive in observing patterns of recurrence is increased use of highly conformal techniques such as proton therapy. We therefore studied geographic distribution of recurrent tumors in relation to the high-risk treatment volume in a cohort of patients with HNSCC receiving combined modality therapy.Methods: Medical records of 508 patients diagnosed with HNSCC in 2010-2015 were reviewed. We identified a subgroup that had local and/or regional recurrence at hybrid positron emission tomography (PET)/computed tomography (CT) and/or magnetic resonance imaging (MRI). We adapted p16 as a surrogate marker for HPV-positivity and only patients with known p16 status were eligible for a detailed analysis where recurrent tumor was copied on the planning CT and the dose received by the recurrent tumor volume was determined using dose-volume histograms.Results: Twenty-five patients who had received either cisplatin (n = 23) or cetuximab-enhanced (n = 2) RT were identified. 31 locoregional recurrent tumors were detected among 18 p16 negative and 7 p16 positive patients. Of recurrent tumors 14 (45%) were classified as in-field, 5 (16%) as marginal miss, and 12 (39%) as true miss. p16 positive patients had 4 in-field, 2 marginal, and 1 true miss. By contrast, p16 negative patients had 10 in-field, 3 marginal, and 11 true miss recurrences.Conclusions: Both p16 positive and negative HNSCC recur in high-risk treatment volume despite the common view of high radiosensitivity of the former. Biomarkers predicting radioresistance should be characterized in p16 positive tumors before widely embarking on de-escalated CRT protocols. Another concern is how to decrease the number of true or marginal misses in p16 negative cases despite multimodality imaging-based target delineation.</p

Dosimetric Comparison and Evaluation of 4 Stereotactic Body Radiotherapy Techniques for the Treatment of Prostate Cancer

Purpose: The aim of this study was to compare dosimetric characteristics, monitor unit, and delivery efficiency of 4 different stereotactic body radiotherapy techniques for the treatment of prostate cancer. Methods: This study included 8 patients with localized prostate cancer. Dosimetric assets of 4 delivery techniques for stereotactic body radiotherapy were evaluated: robotic CyberKnife, noncoplanar intensity-modulated radiotherapy, and 2 intensity-modulated arc therapy techniques (RapidArc and Elekta volumetric-modulated arc therapy). All the plans had equal treatment margins and a prescription dose of 35 Gy in 5 fractions. Results: Statistically significant differences were observed in homogeneity index and mean doses of bladder wall and penile bulb, all of which were highest with CyberKnife. No significant differences were observed in the mean doses of rectum, with values of 15.2+ 2.6, 13.3 +2.6, 13.1 +2.8, and 13.8 +1.6 Gy with CyberKnife, RapidArc, volumetric-modulated arc therapy, and noncoplanar intensity-modulated radiotherapy, respectively. The highest dose conformity was realized with RapidArc. The dose coverage of the planning target volume was lowest with noncoplanar intensity-modulated radiotherapy. Treatment times and number of monitor units were largest with CyberKnife (on average 34.0 + 5.0 minutes and 8704 + 1449 monitor units) and least with intensity-modulated arc therapy techniques (on average 5.1 + 1.1 minutes and 2270 + 497 monitor units).Conclusion: Compared to CyberKnife, the RapidArc, volumetric-modulated arc therapy, and noncoplanar intensity-modulated radiotherapy produced treatment plans with similar dosimetric quality, with RapidArc achieving the highest dose conformity. Overall, the dosimetric differences between the studied techniques were marginal, and thus, the choice of the technique should rather focus on the delivery accuracies and dose delivery times.</p

Aivokasvainten hoito ja moniammatillinen neuro-onkologiaryhmä

Kallonsisäisissä kasvaimissa haasteet kuvantamisessa, molekyylipatologiassa ja hoidonvasteen arvioinnissa ovat suurempia kuin monissa yleisemmissä syövissä. Hiljattainpäivitetty molekyylimuutoksiin perustuva WHO:n keskushermoston kasvainten luokitteluon oleellinen sekä hoidon valinnassa että haittavaikutusten riskin arviossa. Neuro-onkologiaryhmässäneurokirurgi, syöpälääkäri, neurologi, neuroradiologi ja -patologi täydentävät toistensaerityisosaamista. Monialainen hoidon suunnittelu parantaa ja yhdenmukaistaa laatuaja mahdollisesti ennustetta, vaikka näyttö aikuisten glioomassa on vasta alustavaa.Ryhmän ohjeistama seuranta helpottaa ymmärtämään hoitojen vaikutusta potilaan toimintakyvynsäilyttämiseen. Samalla ryhmä saa palautetta hoidon tehosta ja viiveet vähenevät,kun koordinoidaan diagnostiikka ja hoidon toteutus kansainvälisiä ja kansallisia suosituksianoudattaen. Palaute on keskeistä neuro-onkologisen hoidon vaikuttavuuden ja laadunkehittämiselle.</p

Validation of automated magnetic resonance image segmentation for radiation therapy planning in prostate cancer

Background and purposeMagnetic resonance imaging (MRI) is increasingly used in radiation therapy planning of prostate cancer (PC) to reduce target volume delineation uncertainty. This study aimed to assess and validate the performance of a fully automated segmentation tool (AST) in MRI based radiation therapy planning of PC.Material and methodsPelvic structures of 65 PC patients delineated in an MRI-only workflow according to established guidelines were included in the analysis. Automatic vs manual segmentation by an experienced oncologist was compared with geometrical parameters, such as the dice similarity coefficient (DSC). Fifteen patients had a second MRI within 15 days to assess repeatability of the AST for prostate and seminal vesicles. Furthermore, we investigated whether hormonal therapy or body mass index (BMI) affected the AST results.ResultsThe AST showed high agreement with manual segmentation expressed as DSC (mean, SD) for delineating prostate (0.84, 0.04), bladder (0.92, 0.04) and rectum (0.86, 0.04). For seminal vesicles (0.56, 0.17) and penile bulb (0.69, 0.12) the respective agreement was moderate. Performance of AST was not influenced by neoadjuvant hormonal therapy, although those on treatment had significantly smaller prostates than the hormone-naïve patients (p ConclusionFully automated MRI segmentation tool showed good agreement and repeatability compared with manual segmentation and was found clinically robust in patients with PC. However, manual review and adjustment of some structures in individual cases remain important in clinical use.</p

A multi-institutional analysis of a general pelvis continuous Hounsfield unit synthetic CT software for radiotherapy

Purpose To validate a synthetic computed tomography (sCT) software with continuous HUs and large field-of-view (FOV) coverage for magnetic resonance imaging (MRI)-only workflow of general pelvis anatomy in radiotherapy (RT).Methods An sCT software for general pelvis anatomy (prostate, rectum, and female pelvis) has been developed by Philips Healthcare and includes continuous HUs assignment along with large FOV coverage. General pelvis sCTs were generated using a two-stack T1-weighted mDixon fast-field echo (FFE) sequence with a superior-inferior coverage of 36 cm. Seventy-seven prostate, 43 rectum, and 27 gynecological cases were scanned by three different institutions. mDixon image quality and sCTs were evaluated for soft tissue contrast by using a confidence level scale from 1 to 5 for bladder, prostate/rectum interface, mesorectum, and fiducial maker visibility. Dosimetric comparison was performed by recalculating the RT plans on the sCT after rigid registration. For 12 randomly selected cases, the mean absolute error (MAE) between sCT and CT was calculated to evaluate HU similarity, and the Pearson correlation coefficients (PCC) between the CT- and sCT-generated digitally reconstructed radiographs (DRRs) were obtained for quantitative comparison. To examine geometric accuracy of sCT as a reference for cone beam CT (CBCT), the difference between bone-based alignment of CBCT to CT and CBCT to sCT was obtained for 19 online-acquired CBCTs from three patients.Results Two-stack mDixon scans with large FOV did not show any image inhomogeneity or fat-water swap artifact. Fiducials, Foley catheter, and even rectal spacer were visible as dark signal on the sCT. Average visibility confidence level (average +/- standard deviation) on the sCT was 5.0 +/- 0.0, 4.6 +/- 0.5, 3.8 +/- 0.4, and 4.0 +/- 1.1 for bladder, prostate/rectum interface, mesorectum and fiducial markers. Dosimetric accuracy showed on average < 1% difference with the CT-based plans for target and normal structures. The MAE of bone and soft tissue between the sCT and CT are 120.9 +/- 15.4 HU, 33.4 +/- 4.1 HU, respectively. Average PCC of all evaluated DRR pairs was 0.975. The average offset between CT and sCT as reference was (LR, AP, SI) = (0.19 +/- 0.35, 0.14 +/- 0.60, 0.44 +/- 0.54) mm.Conclusions The continuous HU sCT software-generated realistic sCTs and DRRs to enable MRI-only planning for general pelvis anatomy

Repeatability of tumour hypoxia imaging using [18F]EF5 PET/CT in head and neck cancer

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68Ga-Citrate Positron Emission Tomography of Healthy Men: Whole-Body Biodistribution Kinetics and Radiation Dose Estimates

68Ga-citrate has one of the simplest chemical structures of all 68Ga-radiopharmaceuticals, and its clinical use is justified by the proven medical applications using its isotope-labeled compound 67Ga-citrate. To support broader application of 68Ga-citrate in medical diagnosis, further research is needed to gain clinical data from healthy volunteers. In this work, we studied the biodistribution of 68Ga-citrate and subsequent radiation exposure from it in healthy males. Methods: 68Ga-citrate was prepared with an acetone-based radiolabeling procedure compliant with Good Manufacturing Practices. Six healthy males (age 41 ± 12 years, mean ± SD) underwent sequential whole-body PET/CT scans after an injection of 204 ± 8 MBq of 68Ga-citrate. Serial arterialized venous blood samples were collected during PET imaging and the radioactivity concentration was measured with a gamma counter. Urinary voids were collected and measured. The Medical Internal Radiation Dose (MIRD) bladder-voiding model with a 3.5 hour voiding interval was used. A model using a 70 kg adult male and MIRD schema was used to estimate absorbed doses in target organs and effective doses. Calculations were performed using OLINDA/EXM 2.0 software. Results: Radioactivity clearance from the blood was slow, and relatively high radioactivity concentrations were observed over the whole of the 3 hour measuring period. Although radioactivity excretion via urine was rather slow (biological half-time, 69 ± 24 hours), the highest decay-corrected concentrations in urinary bladder contents were measured at 90 and 180 minute time points. Moderate concentrations were also seen in kidneys, liver, and spleen. The source organs showing the largest residence times were muscle, liver, lung, and heart contents. The heart wall received the highest absorbed dose of 0.077 ± 0.008 mSv/MBq. The mean effective dose (ICRP 103) was 0.021 ± 0.001 mSv/MBq. Conclusion: PET imaging with 68Ga-citrate is associated with modest radiation exposure. A 200 MBq injection of 68Ga-citrate results in an effective radiation dose of 4.2 mSv, which is in the same range as other 68Ga-labeled tracers. This suggests the feasibility of clinical studies using 68Ga-citrate imaging in humans and the possibility of performing multiple scans in the same subjects across the course of a year.</p

First-in-Human Study of 68 Ga-DOTA-Siglec-9, PET Ligand Targeting Vascular Adhesion Protein 1

Sialic acid-binding immunoglubulin-like lectin 9 (Siglec-9) is a ligand of vascular adhesion protein 1 (VAP-1). A gallium 68-labeled peptide of Siglec-9, 68Ga-DOTA-Siglec-9, holds promise as a novel PET tracer for imaging of inflammation. This first-in-human study investigated the safety, tolerability, biodistribution, and radiation dosimetry of this radiopharmaceutical. Methods: Six healthy males underwent dynamic whole-body PET/CT. Serial venous blood samples were drawn from 1-240 min after intravenous injection of 162 ± 4 MBq of 68Ga-DOTA-Siglec-9. In addition to gamma counting, the plasma samples were analyzed by high-performance liquid chromatography to detect intact tracer and radioactive metabolites. Radiation doses were calculated using the OLINDA/EXM 2.2 software. In addition, a patient with early rheumatoid arthritis was studied with both 68Ga-DOTA-Siglec-9 and 18F-FDG PET/CT to determine the ability of the new tracer to detect arthritis. Results: 68Ga-DOTA-Siglec-9 was well tolerated by all subjects. 68Ga-DOTA-Siglec-9 was rapidly cleared from blood circulation and several radioactive metabolites were detected. The organs with the highest absorbed doses were the urinary bladder wall (0.38 mSv/MBq) and kidneys (0.054 mSv/MBq). The mean effective dose was 0.022 mSv/MBq (range 0.020-0.024 mSv/MBq). Most importantly, however, 68Ga-DOTA-Siglec-9 was able to detect arthritis comparable to 18F-FDG. Conclusion: Intravenous injection of 68Ga-DOTA-Siglec-9 was safe and biodistribution is favorable for testing of the tracer in larger group of patients with rheumatoid arthritis planned in the next phase of clinical trials. The effective radiation dose of 68Ga-DOTA-Siglec-9 was within the same range as those of other 68Ga-labeled tracers. Injection of 150 MBq of 68Ga-DOTA-Siglec-9 would expose a subject to 3.3 mSv. These findings support the possible repeated clinical use of 68Ga-DOTA-Siglec-9, e.g., in trials aiming to elucidate the treatment efficacy of novel drug candidates