Smaller Planning Target Volume Research Articles

Comprehensive stereotactic radiosurgery platform characterization: A novel end-to-end approach with anthropomorphic 3D dosimetry.

Stereotactic radiosurgery (SRS) is a widely employed strategy for intracranial metastases, utilizing linear accelerators and volumetric modulated arc therapy (VMAT). Ensuring precise linear accelerator performance is crucial, given the small planning target volume (PTV) margins. Rapid dose falloff is vital to minimize brain radiation necrosis. Despite advances in SRS planning, tools for end-to-end testing of SRS treatments are lacking, hindering confidence in the procedure. This study introduces a novel end-to-end three-dimensional (3D) anthropomorphic dosimetry system for characterization of a radiosurgery platform, aiming to measure planning metrics, dose gradient index (DGI), brain volumes receiving at least 10 and 12Gy (V10, V12), as well as assess delivery uncertainties in multitarget treatments. The study also compares metrics from benchmark plans to enhance understanding and confidence in SRS treatments. The developed anthropomorphic 3D dosimetry system includes a modified Stereotactic End-to-End Verification (STEEV) phantom with a customized insert integrating 3D dosimeters and a fiber optic CT scanner. Labview and MATLAB programs handle optical scanning, image preprocessing, and dosimetric analysis. SlicerRT is used for 3D dose visualization and analysis. A film stack insert was used to validate the 3D dosimeter measurements at specific slices. Benchmark plans were developed and measured to investigate off-axis errors, dose spillage, small field dosimetry, and multi-target delivery. The accuracy of the developed 3D dosimetry system was rigorously assessed using radiochromic films. Two two-dimensional (2D) dose planes, extracted from the 3D dose distribution, were compared with film measurements, resulting in high passing rates of 99.9% and 99.6% in gamma tests. The mean relative dose difference between film and 3D dosimeter measurements was -1%, with a standard deviation of 2.2%, well within dosimeter uncertainties. In the first module, evaluating single-isocenter multitarget treatments, a 1.5mm dose distribution shift was observed when targets were 7cm off-axis. This shift was attributed to machine mechanical errors and image-guided system uncertainties, indicating potential limitations in conventional gamma tests. The second module investigated discrepancies in intermediate-to-low dose spillage, revealing higher measured doses in the connecting region between closely positioned targets. This discrepancy was linked to uncertainties in treatment planning system (TPS) modeling of out-of-field dose and multileaf collimator (MLC) characteristics, resulting in lower DGI values and higher V10 and V12 values compared to TPS calculations. In the third module, irradiating multiple targets showed consistent V10 and V12 values within 1 cm3 agreement with dose calculations. However, lower DGI values from measurements compared to calculations suggested intricacies in the treatment process. Conducting vital end-to-end testing demonstrated the anthropomorphic 3D dosimetry system's capacity to assess overall treatment uncertainty, offering a valuable tool for enhancing treatment accuracy in radiosurgery platforms. The study introduces a novel anthropomorphic 3D dosimetry system for end-to-end testing of a radiosurgery platform. The system effectively measures plan quality metrics, captures mechanical errors, and visualizes dose discrepancies in 3D space. The comprehensive evaluation capability enhances confidence in the commissioning and verification process, ensuring patient safety. The system is recommended for commissioning new radiosurgery platforms and remote auditing of existing programs.

Assessing the adequacy of a 5-mm planning target volume margin for 4D-CT scan-based image-guided radiotherapy for locally advanced carcinoma of the lung

In developed nations, 4D-computed tomography (4D-CT)-based image-guided radiotherapy (IGRT) has become the standard for treating lung carcinoma patients, with the primary goal of achieving disease cure. However, its usage in India remains limited. Here, we compared target volume delineation for radical radiation planning in patients with locally advanced lung carcinoma using helical free-breathing CT (FBCT) and 4D-CT. In addition, we assessed the adequacy of a 5-mm planning target volume (PTV) margin with 4D-CT planning. Fifty patients with locally advanced lung cancer were enrolled in the study. Each patient underwent contouring based on 4D-CT to generate an internal target volume, and a 5-mm PTV margin (PTV_4D) was added for radical radiation. Subsequently, each patient underwent two intensity-modulated radiation therapy (IMRT) plans with comparable planning and optimization parameters. One plan was based on the FBCT-based volume (PTV_3D), while the other was based on the 4D-CT-based volume (PTV_4D). PTV, organ at risk (OAR) dose, and PTV coverage by 95% of the prescribed dose (PTVD 95_3D vs. PTVD 95_4D) were compared between the two schemes. Results revealed that 4D-CT-based planning reduced PTV (mean PTV volume: 539 cc vs. 782 cc) and lowered OAR doses (mean lung dose: 13 Gy vs. 15 Gy; mean esophagus dose: 18.5 Gy vs. 21.15 Gy; mean spinal cord max dose: 35.59 Gy vs. 37.39 Gy). At 3 months after treatment imaging, 40% of the patients showed a complete response, 48% showed a partial response, 4% showed stable disease, and 8% showed progressive disease. In conclusion, 4D-CT-based radiation planning for locally advanced lung carcinoma with a reduced PTV margin of 5 mm can dramatically decrease the PTV and OAR doses without sacrificing PTV coverage compared to FBCT-based planning. However, daily online image guidance or at least a well-defined offline image guidance protocol is recommended when employing such a small PTV margin.

Stereotactic body radiotherapy with volumetric intensity-modulated arc therapy and flattening filter-free beams: dosimetric considerations.

The present study comparatively evaluates the impact of energy-matched flattening filter-free (FFF) photon beams with different energy levels on the physical-dosimetric quality of lung and liver stereotactic body radiotherapy (SBRT) treatment plans. For this purpose, 54different lung and liver lesions from 44patients who had already received SBRT combined with volumetric modulated arc therapy (VMAT) were included in this retrospective planning study. Planning computed tomography scans already available were used for the renewed planning with 6MV, 6MV-FFF, 10MV, and 10MV-FFF under constant planning objectives. The treatment delivery data, dosimetric distributions, and dose-volume histograms as well as parameters such as the conformity index and gradient indices were the basis for the evaluation and comparison of treatment plans. Asignificant reduction of beam-on time (BOT) was achieved due to the high dose rates of FFF beams. In addition, we showed that for FFF beams compared to flattened beams of the same energy level, smaller planning target volumes (PTV) require fewer monitor units (MU) than larger PTVs. An equal to slightly superior target volume coverage and sparing of healthy tissue as well as organs at risk in both lung and liver lesions were found. Significant differences were seen mainly in the medium to lower dose range. We found that FFF beams together with VMAT represent an excellent combination for SBRT of lung or liver lesions with shortest BOT for 10MV-FFF but significant dose savings for 6MV-FFF in lung lesions.

Histopathologically confirmed radiation-induced damage of the brain – an in-depth analysis of radiation parameters and spatio-temporal occurrence

BackgroundRadiation-induced damage (RID) after radiotherapy (RT) of primary brain tumors and metastases can be challenging to clinico-radiographically distinguish from tumor progression. RID includes pseudoprogression and radiation necrosis; the latter being irreversible and often associated with severe symptoms. While histopathology constitutes the diagnostic gold standard, biopsy-controlled clinical studies investigating RID remain limited. Whether certain brain areas are potentially more vulnerable to RID remains an area of active investigation. Here, we analyze histopathologically confirmed cases of RID in relation to the temporal and spatial dose distribution.MethodsHistopathologically confirmed cases of RID after photon-based RT for primary or secondary central nervous system malignancies were included. Demographic, clinical, and dosimetric data were collected from patient records and treatment planning systems. We calculated the equivalent dose in 2 Gy fractions (EQD22) and the biologically effective dose (BED2) for normal brain tissue (α/β ratio of 2 Gy) and analyzed the spatial and temporal distribution using frequency maps.ResultsThirty-three patients were identified. High-grade glioma patients (n = 18) mostly received one normofractionated RT series (median cumulative EQD22 60 Gy) to a large planning target volume (PTV) (median 203.9 ccm) before diagnosis of RID. Despite the low EQD22 and BED2, three patients with an accelerated hyperfractionated RT developed RID. In contrast, brain metastases patients (n = 15; 16 RID lesions) were often treated with two or more RT courses and with radiosurgery or fractionated stereotactic RT, resulting in a higher cumulative EQD22 (median 162.4 Gy), to a small PTV (median 6.7 ccm). All (n = 34) RID lesions occurred within the PTV of at least one of the preceding RT courses. RID in the high-grade glioma group showed a frontotemporal distribution pattern, whereas, in metastatic patients, RID was observed throughout the brain with highest density in the parietal lobe. The cumulative EQD22 was significantly lower in RID lesions that involved the subventricular zone (SVZ) than in lesions without SVZ involvement (median 60 Gy vs. 141 Gy, p = 0.01).ConclusionsAccelerated hyperfractionated RT can lead to RID despite computationally low EQD22 and BED2 in high-grade glioma patients. The anatomical location of RID corresponded to the general tumor distribution of gliomas and metastases. The SVZ might be a particularly vulnerable area.

Dosimetric impact of mechanical movements of the Linac gantry during treatments with small fields.

Current accepted linac Quality Assurance (QA) guidelines used for Volumetric Modulated Arc Therapy (VMAT) suggest a mechanical isocentre tolerance level of 1mm. However, this tolerance level has not been well-established for the specific case of small field stereotactic VMAT. This study aims to evaluate the clinical impact of mechanical uncertainty on this treatment modality by modelling systematic gantry sag derived isocentre variance in the Treatment Planning System (TPS). A previously reported dataset of gantry sag values in the literature served as a starting point for this study. Using an in-house developed VMAT arc splitting algorithm, isocentre shifts were applied at a Control Point (CP) level to DICOM-RT treatment plans. Dose distributions for varying isocentre shift magnitudes were calculated for a set of 29 stereotactic VMAT plans using the Eclipse Acuros XB dose algorithm. These plans had a range of Planning Target Volume (PTV) sizes. A quantitative comparison of each plan was conducted by evaluating five Dose Volume Histogram (DVH)-derived plan quality metrics. All metrics exhibited a deterioration in plan quality with increasing magnitudes of isocentre shift. At small PTV sizes, these effects were amplified, exhibiting significant changes at 1mm of average shift when typical targets and tolerances were considered. For plans with PTVs between 0 and 5 cm3, a 1mm shift reduced PTV coverage by 6.6 ± 2.2% and caused a 12.1 ± 3.8% deterioration in the conformity index. Based on the results of this study, the prevalent tolerance of 1mm may not be suitable for treatments of small PTVs with small fields. In contrast to commonly accepted values, an absolute mechanical isocentre of 0.5mm with action level at 0.75mm is recommended for stereotactic VMAT of PTV sizes below 10 cm3.

STereotactic Ablative RadioTherapy in NEWly Diagnosed and Recurrent Locally Advanced Non-Small Cell Lung Cancer Patients Unfit for ConcurrEnt RAdio-Chemotherapy: Early Analysis of the START-NEW-ERA Non-Randomised Phase II Trial

This is a single arm phase 2 trial (Clinical trials.gov NCT05291780) to assess local control (LC) and safety of SAbR in patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC) unfit for concurrent chemo-radiation therapy (ChT-RT). Neoadjuvant ChT was prescribed in fit patients. The tumor volume included primary tumor and any regionally positive node/s. The coprimary study endpoints were LC and safety. Between December 31, 2015, and December 31, 2020, 50 patients with LA-NSCLC were enrolled. Histology was squamous cell carcinoma and adenocarcinoma (ADC) in 52% and 48%, respectively. Forty (80%) patients had ultracentral tumor. Twenty-seven (54%) received neoadjuvant ChT and 7 (14%) adjuvant durvalumab. Median prescribed dose was 45 Gy (range, 35-55) and 40 Gy (35-45) in 5 daily fractions to tumor and node/s, respectively. After a median follow-up of 38 months (range, 12-80), 19 (38%) patients had experienced local recurrence (LR) at a median time of 13 months (range, 7-34). The median LR-free survival (FS) was not reached (95% confidence interval [CI], 28 to not reached). The 1-, 2-, and 3-year LR-FS rates were 86% ± 5%, 66% ± 7%, and 56% ± 8%, respectively. At last follow-up, 33 (66%) patients were alive. Median overall survival (OS) was 55 months (95% CI, 43-55 months). The 1-, 2-, and 3-year OS rates were 94% ± 3%, 79% ± 6%, and 72% ± 7%, respectively. No patients developed ≥ grade (G) 3 toxicity. ADC (hazard ratio [HR], 3.61; 95% CI, 1.15-11.35) was a significant predictor of better LC, while OS was significantly conditioned by smaller planning target volumes (HR, 1.004; 95% CI, 1.001-1.010) and tumor, node, and metastasis stage (HR, 4.8; 95% CI, 1.34-17). Patients with LA-NSCLC treated with SABR had optimal LC and promising OS in absence of ≥G3 toxicity. Our early outcomes would suggest the feasibility of using this approach in patients with LA-NSCLC unfit for concurrent ChT-RT.

Target volume size effect on comparison of dynamic arc treatment plans computed using flattened and unflattened 6MV beams

Introduction/backgroundIn conventional linear accelerators, to obtain flat profiles leading to uniform dose distribution in homogeneous medium, the flattening filter is usually applied on the beam path. In recent years, to obtain higher dose rates, there have been the options of flattening filter free (FFF) beams and it has been noticed that these have many advantages. The aim of this study was to clearly underline the advantages and the drawbacks of flattened filter free (FFF) beams in comparison with the flattening filter (FF) beams for different clinical contexts (planning target volumes locations). MethodsTwo groups (planned with auto-planning VMAT, full and partial arcs) of eight patients each were analyzed: Group I (small planning target volume PTV, with average volume 48.9 ±44.4 cm3), Group II (large PTV, with average volume 532.4 ±368.8 cm3). Both beam modalities 6MV and 6MVFFF were compared in terms of Dmax, D95%, D1cc, D2cc, homogeneity index (HI), number of monitor units (MU), treatment delivery time. ResultsUsing the 6MVFFF, the treatment delivery time was significantly reduced (p<0.05). For larger PTVs, the number of MU increased by more than twice, and the p-value shown a significant difference (p= 0.008). The value of Dmax increased by 4%. On the contrary, for small volumes, the results were quite similar from 6MVFFF to 6MV except some differences in terms of MU. ConclusionIt is recommended to use 6MVFFF beam with small PTV volumes. Dose distributions are almost the same as with 6MV and there is a significant reduction of the treatment delivery time up to 57%. Due to the dose profile shape in FFF mode, the dose is lowered beyond the central axis for the FFF beams, and the additional MU allows the dose to be delivered away from the beam axis.

Safety and Efficacy of Stereotactic Ablative Radiotherapy for Ultra-Central Lung Cancer.

BackgroundUltra-central lung cancer (UCLC) is difficult to achieve surgical treatment. Over the past few years, stereotactic ablative radiotherapy (SABR) or stereotactic body radiotherapy (SBRT) obviously improved the clinical efficacy and survival of UCLC patients. However, the adapted scheme of radiation therapy is still controversial. For this, a single arm retrospective analysis was performed on UCLC patients treated with SBRT.Material and MethodsWe retrospectively studied primary UCLC patients who were treated with SBRT of 56 Gy/6-8f between 2010 and 2018. UCLC was defined as planning target volume (PTV) touching or overlapping the proximal bronchial tree, trachea, esophagus, heart, pulmonary vein, or pulmonary artery within 2 cm around the bronchial tree in all directions.ResultsA total of 58 patients whose median age was 68 years (range, 46-85) were included in our study, 79.3% of whom did not undergo any previous therapy. The median dose of the PTV was 77.8 Gy (range, 43.3-91.8), and the median PTV of tumors was 6.2 cm3 (range, 12.9-265.0). With a median follow-up of 57 months (range, 6-90 months), the median cumulative overall survival (OS) rate was 58 months (range, 2-105). In addition, the 1-year, 2-year and 5-year OS rates were 94.7%, 75.0% and 45.0%, respectively. In our univariable analysis (p=0.020) and multivariate analysis (p=0.004), the OS rate was associated with the PTV. The 5-year OS rates for PTV <53.0 cm3 and PTV ≥53.0 cm3 were 61.6% and 37.4%, respectively. Regarding toxicity after SBRT, there were two cases (3.5%) with grade ≥3 adverse events, of which 1 case died of sudden severe unexplained hemoptysis.ConclusionsPatients with UCLC can benefit from SBRT at a dose of 56 Gy/6-8f. On the other hand, smaller PTV was associated with superior outcomes, and the cure difference needs to be validated by prospective comparative trials.

Accelerated hyper-versus normofractionated radiochemotherapy with temozolomide in patients with glioblastoma: a multicenter retrospective analysis

Background and purposeThe standard treatment of glioblastoma patients consists of surgery followed by normofractionated radiotherapy (NFRT) with concomitant and adjuvant temozolomide chemotherapy. Whether accelerated hyperfractionated radiotherapy (HFRT) yields comparable results to NFRT in combination with temozolomide has only sparsely been investigated. The objective of this study was to compare NFRT with HFRT in a multicenter analysis.Materials and methodsA total of 484 glioblastoma patients from four centers were retrospectively pooled and analyzed. Three-hundred-ten and 174 patients had been treated with NFRT (30 × 1.8 Gy or 30 × 2 Gy) and HFRT (37 × 1.6 Gy or 30 × 1.8 Gy twice/day), respectively. The primary outcome of interest was overall survival (OS) which was correlated with patient-, tumor- and treatment-related variables via univariable and multivariable Cox frailty models. For multivariable modeling, missing covariates were imputed using multiple imputation by chained equations, and a sensitivity analysis was performed on the complete-cases-only dataset.ResultsAfter a median follow-up of 15.7 months (range 0.8–88.6 months), median OS was 16.9 months (15.0–18.7 months) in the NFRT group and 14.9 months (13.2–17.3 months) in the HFRT group (p = 0.26). In multivariable frailty regression, better performance status, gross-total versus not gross-total resection, MGMT hypermethylation, IDH mutation, smaller planning target volume and salvage therapy were significantly associated with longer OS (all p < 0.01). Treatment differences (HFRT versus NFRT) had no significant effect on OS in either univariable or multivariable analysis.ConclusionsSince HFRT with temozolomide was not associated with worse OS, we assume HFRT to be a potential option for patients wishing to shorten their treatment time.

Impact of Target Volume and Image Guidance on Post-Prostatectomy Patients Treated With Intensity Modulated Radiation Therapy

<h3>Purpose/Objective(s)</h3> Post-operative radiotherapy (PORT) is utilized in select prostate cancer patients. IMRT has been associated with improved dosimetry and acute toxicity. Smaller treatment margins for PORT have been recommended when using image guidance (IG), which has also been associated with reduced toxicity. Compared to intact prostate IG-IMRT, however, PORT is delivered to a space at risk for recurrence with no grossly visible target, so using targeted conformal techniques with less margin for error may compromise tumor control. Our institution initiated IG-IMRT for PORT in 2005 and adopted larger planning target volumes (PTV) in 2012. We hypothesized that smaller PTV and surgical clip-based IG-IMRT associate with increased biochemical failure (BF). <h3>Materials/Methods</h3> Patients who underwent post-prostatectomy IG-IMRT without concurrent androgen deprivation therapy (ADT) from 1/2005 to 12/2016 were included, with division into pre-2012 and post-2012 cohorts. Demographics and tumor/treatment variables were recorded retrospectively. Oncologic outcomes included BF (initiation of ADT and/or PSA > 0.2 ng/ml and rising) and late toxicities (defined by RTOG criteria, occurring > 90 days after RT). <h3>Results</h3> 133 patients met criteria: 73 treated pre-2012 and 60 treated post-2012, with a median follow-up of 5 and 9 years, respectively. Compared to the pre-2012 cohort, patients in the post-2012 cohort were more often treated with salvage vs adjuvant RT (<i>P</i> = 0.007), and had higher pre-PORT PSA (0.38 vs 0.20, <i>P</i> = 0.01). 5-year BF did not differ between cohorts (36% vs 43%, <i>P</i> = 0.48). Pre-2012, a smaller percentage of patients underwent on-treatment alignment to surgical clips (40% vs 58%, <i>P</i> = 0.033), vs bony anatomy. Alignment to surgical clips was associated with increased BF in the pre-2012 cohort (HR 2.13, <i>P</i> = 0.041) but not in the post-2012 cohort. Notably, significantly more patients received IG with CBCT in the post-2012 cohort (82% vs 33%). Pre-2012, the median PTV was 198.63 cc versus 242.59 cc post-2012 (<i>P</i> = 0.002). Among the entire cohort on univariate analysis, however, clinical target volume (CTV), CTV-PTV ratio and PTV as continuous variables were not associated with increased risk of BF. Late toxicities were not different between the two cohorts. <h3>Conclusion</h3> This retrospective analysis reports on toxicity and oncologic outcomes of post-prostatectomy patients treated with IG-IMRT. Despite changes in tumor/treatment characteristics, dosimetric parameters, and image guidance techniques, toxicity and cancer-related outcomes remain similar over a 7-year period. Clip-based IG-IMRT in conjunction with small target volumes may be associated with higher risk of BF, and use of CBCT IG may offset this risk. Additional dosimetric and treatment analyses will be presented. These findings should be validated in prospective datasets.

Feasibility of Conebeam CT-based online adaptive radiotherapy for neoadjuvant treatment of rectal cancer

BackgroundOnline adaptive radiotherapy has the potential to reduce toxicity for patients treated for rectal cancer because smaller planning target volumes (PTV) margins around the entire clinical target volume (CTV) are required. The aim of this study is to describe the first clinical experience of a Conebeam CT (CBCT)-based online adaptive workflow for rectal cancer, evaluating timing of different steps in the workflow, plan quality, target coverage and patient compliance.MethodsTwelve consecutive patients eligible for 5 × 5 Gy pre-operative radiotherapy were treated on a ring-based linear accelerator with a multidisciplinary team present at the treatment machine for each fraction. The accelerator is operated using an integrated software platform for both treatment planning and delivery. In all directions for all CTVs a PTV margin of 5 mm was used, except for the cranial/caudal borders of the total CTV where a margin of 8 mm was applied. A reference plan was generated based on a single planning CT. After aligning the patient the online adaptive procedure started with acquisition of a CBCT. The planning CT scan was registered to the CBCT using deformable registration and a synthetic CT scan was generated. With the support of artificial intelligence, structure guided deformation and the synthetic CT scan contours were adapted by the system to match the anatomy on the CBCT. If necessary, these contours were adjusted before a new plan was generated. A second and third CBCT were acquired to validate the new plan with respect to CTV coverage just before and after treatment delivery, respectively. Treatment was delivered using volumetric modulated arc treatment (VMAT). All steps in this process were defined and timed.ResultsOn average the timeslot needed at the treatment machine was 34 min. The process of acquiring a CBCT, evaluating and adjusting the contours, creating the new plan and verifying the CTV on the CBCT scan took on average 20 min. Including delivery and post treatment verification this was 26 min. Manual adjustments of the target volumes were necessary in 50% of fractions. Plan quality, target coverage and patient compliance were excellent.ConclusionsFirst clinical experience with CBCT-based online adaptive radiotherapy shows it is feasible for rectal cancer.Trial registration Medical Research Involving Human Subjects Act (WMO) does not apply to this study and was retrospectively approved by the Medical Ethics review Committee of the Academic Medical Center (W21_087 # 21.097; Amsterdam University Medical Centers, Location Academic Medical Center, Amsterdam, The Netherlands).

Dosimetric comparison of MR-linac-based IMRT and conventional VMAT treatment plans for prostate cancer

BackgroundThe aim of this study was to evaluate and compare the performance of intensity modulated radiation therapy (IMRT) plans, planned for low-field strength magnetic resonance (MR) guided linear accelerator (linac) delivery (labelled IMRT MRL plans), and clinical conventional volumetric modulated arc therapy (VMAT) plans, for the treatment of prostate cancer (PCa). Both plans used the original planning target volume (PTV) margins. Additionally, the potential dosimetric benefits of MR-guidance were estimated, by creating IMRT MRL plans using smaller PTV margins.Materials and methods20 PCa patients previously treated with conventional VMAT were considered. For each patient, two different IMRT MRL plans using the low-field MR-linac treatment planning system were created: one with original (orig.) PTV margins and the other with reduced (red.) PTV margins. Dose indices related to target coverage, as well as dose-volume histogram (DVH) parameters for the target and organs at risk (OAR) were compared. Additionally, the estimated treatment delivery times and the number of monitor units (MU) of each plan were evaluated.ResultsThe dose distribution in the high dose region and the target volume DVH parameters (D98%, D50%, D2% and V95%) were similar for all three types of treatment plans, with deviations below 1% in most cases. Both IMRT MRL plans (orig. and red. PTV margins) showed similar homogeneity indices (HI), however worse values for the conformity index (CI) were also found when compared to VMAT. The IMRT MRL plans showed similar OAR sparing when the orig. PTV margins were used but a significantly better sparing was feasible when red. PTV margins were applied. Higher number of MU and longer predicted treatment delivery times were seen for both IMRT MRL plans.ConclusionsA comparable plan quality between VMAT and IMRT MRL plans was achieved, when applying the same PTV margin. However, online MR-guided adaptive radiotherapy allows for a reduction of PTV margins. With a red. PTV margin, better sparing of the surrounding tissues can be achieved, while maintaining adequate target coverage. Nonetheless, longer treatment delivery times, characteristic for the IMRT technique, have to be expected.

Outcomes after stereotactic radiosurgery of brain metastases in patients with malignant melanoma and validation of the melanoma molGPA

IntroductionMalignant melanoma is the third most common primary in the diagnosis of brain metastases. Stereotactic radiosurgery (SRS) is a well-established treatment option in limited brain disease. We analyzed outcomes of SRS with a particular focus on the graded prognostic assessment (GPA, melanoma molGPA), prognostic factors, and toxicity.MethodsWe evaluated 173 brain metastases in 83 patients with malignant melanoma. All were treated with SRS median dose of 20 Gy prescribed to the 80 or 100% isodose line between 2002 and 2019. All patients were followed-up regularly, including contrast‐enhanced brain imaging as well as clinical examination, initially 6 weeks after treatment, then in quarterly follow-up.ResultsThe median age was 61 years (range 27–80); 36 female and 47 male patients were treated. After a median follow-up of 5.7 months, median OS (overall survival) was 9.7 months 95%-KI 4.7–14.7). LC (local control) at 6 months, 12, 24 months was 89%, 86%, and 72%, respectively (median was not reached). Median DBC (distant brain control) was 8.2 months (95%-KI 4.7–11.7). For OS, a KPS ≥ 80%, a positive BRAF mutation status, a small PTV (planning target volume), the absence of extracranial metastases, as well as a GPA and melanoma molGPA > 2 were prognostic factors. In the MVA, a small PTV and a melanoma molGPA > 2 remained significant.ConclusionThe present survival outcomes support the use of the disease-specific melanoma molGPA as reliable prognostic score. Favorable outcomes for SRS compared to other studies were observed. In the treatment of brain metastases of malignant melanoma patients, a multidisciplinary approach consisting of surgery, SRS, chemotherapy, and immunotherapy should be considered.

Automatic Segmentation Using Deep Learning to Enable Online Dose Optimization During Adaptive Radiation Therapy of Cervical Cancer

This study investigated deep learning models for automatic segmentation to support the development of daily online dose optimization strategies, eliminating the need for internal target volume expansions and thereby reducing toxicity events of intensity modulated radiation therapy for cervical cancer. The cervix-uterus, vagina, parametrium, bladder, rectum, sigmoid, femoral heads, kidneys, spinal cord, and bowel bag were delineated on 408 computed tomography (CT) scans from patients treated at MD Anderson Cancer Center (n = 214), Polyclinique Bordeaux Nord Aquitaine (n = 30), and enrolled in a Medical Image Computing & Computer Assisted Intervention challenge (n= 3). The data were divided into 255 training, 61 validation, 62 internal test, and 30 external test CT scans. Two models were investigated: the 2-dimensional (2D) DeepLabV3+ (Google) and 3-dimensional (3D) Unet in RayStation (RaySearch Laboratories). Three intensity modulated radiation therapy plans were generated on each CT of the internal and external test sets using either the manual, 2D model, or 3D model segmentations. The dose constraints followed the External beam radiochemotherapy and MRI based adaptive BRAchytherapy in locally advanced CErvical cancer (EMBRACE) II protocol, with reduced margins of 5 and 3 mm for the target and nodal planning target volume. Geometric discrepancies between the manual and predicted contours were assessed using the Dice similarity coefficient (DSC), distance-to-agreement, and Hausdorff distance. Dosimetric discrepancies between the manual and model doses were assessed using clinical indices on the manual contours and the gamma index. Interobserver variability was assessed for the cervix-uterus, parametrium, and vagina for the definition of the primary clinical target volume (CTVT) on the external test set. Average DSCs across all organs were 0.67 to 0.96, 0.71 to 0.97, and 0.42 to 0.92 for the 2D model and 0.66 to 0.96, 0.70 to 0.97, and 0.37 to 0.93 for the 3D model on the validation, internal, and external test sets. Average DSCs of the CTVT were 0.88 and 0.81 for the 2D model and 0.87 and 0.82 for the 3D model on the internal and external test sets. Interobserver variability of the CTVT corresponded to a mean (range) DSC of 0.85 (0.77-0.90) on the external test set. On the internal test set, the doses from the 2D and 3D model contours provided a CTVT V42.75 Gy >98% for 98% and 91% of the CT scans, respectively. On the external test set, these percentages were increased to 100% and 93% for the 2D and 3D models, respectively. The investigated models provided auto-segmentation of the cervix anatomy with similar performances on 2 institutional data sets and reasonable dosimetric accuracies using small planning target volume margins, paving the way to automatic online dose optimization for advanced adaptive radiation therapy strategies.

Carbon ion radiotherapy for sacral chordoma: A retrospective nationwide multicentre study in Japan

Background and purposeUsefulness of carbon ion radiotherapy (CIRT) for sacral chordoma has been reported from single institutions. We conducted a retrospective nationwide multicentre study to evaluate the clinical outcomes of CIRT for sacral chordoma in Japan. Materials and methodsA total of 219 patients who underwent CIRT for sacral chordoma at institutions across Japan between December 2003 and July 2014 were included in this study. ResultsMedian patient age was 67 years (range, 26–87 years). Most patients had no history of surgical resection (96%). The most frequent planning target volume (PTV) range was 100–500 mL (65%). The most frequently used dose-fractionation was 67.2 Gy (relative biological effectiveness) in 16 fractions (65%). The median follow-up was 56 months (range, 7–132 months). The 5-year overall survival (OS), progression-free survival, and local control rates were 84%, 48%, and 72%, respectively. Frequent sites of out-of-field recurrence included bone (9%) and lung (9%) metastases. The Cox proportional hazards model revealed that both younger age (P = 0.004) and smaller PTV (P = 0.001) were associated with significantly better OS. Acute toxicities of ≥Grade 3 occurred in eight patients (4%). Late toxicities of ≥Grade 3 occurred in 13 patients (6%): skin disorders in six patients (3%), pain in three (1%), myositis in three (1%), etc. ConclusionOur retrospective nationwide multicentre study showed that CIRT for sacral chordoma was effective and safe, and replicated the previously reported data from a representative CIRT institution in Japan demonstrating high local control and low toxicity rates.

Lung optimized treatment with CyberKnife® in inoperable lung cancer patients: feasibility analysis of a mono-institutional 115 patient series.

CyberKnife® Lung Optimized Treatment (LOT) allows the treatment of lung cancer without invasive fiducial implantation. The aim of this retrospective analysis was to evaluate the feasibility, toxicity and clinical outcome. One hundred fifteen patients (124 lesions) were treated with CyberKnife® using LOT. The median age was 72.6 years (range 31.8-90.3). From 124 treated lesions, 52 were with histopathological confirmation (41 primitive pulmonary cancers, 8 pulmonary metastases) and 72 as untyped tumors. For 5 patients (6 lesions) treatment was an in-field re-irradiation. Concomitant therapy was administered in 7 patients. Zero-View tracking was applied in 69 patients, 1-View in 33 patients, 2-View in 22 patients. The median total dose was 45 Gy (range 18-54), median dose/fraction was 15 Gy (range 4-18) with a median prescription isodose of 80% (range 68-85). The median planning target volume (PTV) was 25 cm3 (range 3-195). The median follow-up was 20 months (range 7-47). Thirty-seven patients (32%) were alive with no evidence of disease, 39 patients (34%) were alive with clinically evident disease, and 38 patients (33%) died of the disease. The 1- and 2-year overall survival (OS) rate was 83% and 61%. The median time to progression was 19 months (95% confidence interval: 11-19 months), 1- and 2-year progression-free survival (PFS) rates were 62% and 41%, respectively. Smaller PTV was significantly associated with better OS, PFS and in-field PFS in univariate and multivariate analyses. Acute toxicity was observed in 36 patients (41%). Late toxicity was registered in 25 patients (29%). G3 late toxicity was observed in one patient (1.1%). Our data suggest that fiducial less-stereotactic body radiation therapy (SBRT) is a feasible, well-tolerated and potentially effective treatment with high compliance in the setting of inoperable patients due to concomitant disease or previous treatments.

Does “5+5” Equal Better Radiation Treatment Plans in Head and Neck Cancers?

Abstract Purpose Accurate contouring in head and neck cancer (HNC) is critical. International consensus guidelines recommend the 5 + 5 mm rule for expansions around the primary tumor, wherein high- and low-dose clinical target volumes (CTV-P1 and CTV-P2, respectively) are created using successive 5 mm expansions on the gross tumor volume. To our knowledge, the necessity of a low-dose CTV-P2 has never been assessed; therefore, we evaluated the dosimetric impact of adding a CTV-P2 expansion using the 5 + 5 mm rule compared with contouring with a high-dose CTV-P1 alone. Methods and materials A retrospective study of clinically delivered (chemo)radiation therapy treatment plans for HNC was conducted. All patients were treated with 70 Gy in 35 fractions using volumetric modulated arc therapy in a single phase. CTV-P2 was retrospectively contoured per guidelines as a 5 mm expansion on CTV-P1 from the clinical plan, carving off specified barriers to spread. We used a 5 mm planning target volume (PTV) expansion. Our primary outcome was whether 95% of the volume of the PTV for the CTV-P2 contour (ie, PTV-P2) received at least 56 Gy. To assess dose falloff, the coverage of a PTV ring structure was created by subtracting PTV-P1 from PTV-P2. Results Twenty-seven patients from 4 HNC subsites (base of tongue, tonsil, hypopharynx, and supraglottic larynx) were included. In all 108 treatment plans, at least 95% of the PTV-P2 structure received at least 56 Gy. The minimum volume of the PTV-P2 structure receiving at least 56 Gy was 97.4%. Eight of 108 treatment plans had borderline coverage of the PTV ring substructure alone. Conclusions Adding a CTV-P2 structure using the 5 + 5 mm rule had no dosimetric impact, adds contouring time, adds treatment planning complexity, and could potentially introduce errors. The 5 + 5 mm rule may have value in other settings, such as when smaller PTV margins are used, and warrants further evaluation with prospective or randomized studies.

Patterns of re-irradiation for recurrent gliomas and validation of a prognostic score

Purpose or objectiveRe-irradiation is a generally accepted method for salvage treatment in patients with recurrent glioma. However, no standard radiation regimen has been defined. This study aims to compare the efficacy and safety of different treatment regimens and to independently externally validate a recently published reirradiation risk score. Material and methodsWe retrospectively analyzed a cohort of patients with recurrent malignant glioma treated with salvage conventionally fractionated (CFRT), hypofractionated (HFRT) or stereotactic radiotherapy (SRT) between 2007 and 2017 at the University Medical Centers in Utrecht and Groningen. ResultsOf the 121 patients included, 60 patients (50%) underwent CFRT, 22 (18%) HFRT and 39 (32%) SRT. The primary tumor was grade II-III in 52 patients and grade IV in 69 patients with median Overall Survival (mOS) since first surgery of 113 [Interquartile range: 53.2–137] and 39.7 [24.6–64.9] months respectively (p < 0.01). Overall, mOS from the first day of re-irradiation was 9.7 months [6.5–14.6]. No significant difference in mOS was found between the treatment groups. In multivariate analysis, the Karnofsky performance scale ≥70% (p < 0.01), re-irradiation for first recurrence (p = 0.02), longer time interval between RT start dates (p < 0.01) and smaller planning target volume (p < 0.05) were significant favorable prognostic factors. The reirradiation risk score was validated. ConclusionIn our series, mOS after reirradiation was sufficient to justify use of this modality. Until a reliable treatment decision tool is developed based on larger retrospective research, the decision for re-irradiation schedule should remain personalized and based on a multidisciplinary evaluation of each patient.

Generating amorphous target margins in radiation therapy to promote maximal target coverage with minimal target size

Background and significanceThis work provides proof-of-principle for two versions of a heuristic approach that automatically creates amorphous radiation therapy planning target volume (PTV) margins considering local effects of tumor shape and motion to ensure adequate voxel coverage with while striving to minimize PTV size. The resulting target thereby promotes disease control while minimizing the risk of normal tissue toxicity. MethodsThis work describes the mixed-PDF algorithm and the independent-PDF algorithm which generate amorphous margins around a radiation therapy target by incorporating user-defined models of target motion. Both algorithms were applied to example targets – one circular and one “cashew-shaped.” Target motion was modeled by four probability density functions applied to the target quadrants. The spatially variant motion model illustrates the application of the algorithms even with tissue deformation. Performance of the margins was evaluated in silico with respect to voxelized target coverage and PTV size, and was compared to conventional techniques: a threshold-based probabilistic technique and an (an)isotropic expansion technique. To demonstrate the algorithm's clinical utility, a lung cancer patient was analyzed retrospectively. For this case, 4D CT measurements were combined with setup uncertainty to compare the PTV from the mixed-PDF algorithm with a PTV equivalent to the one used clinically. ResultsFor both targets, the mixed-PDF algorithm performed best, followed by the independent-PDF algorithm, the threshold algorithm, and lastly, the (an)isotropic algorithm. Superior coverage was always achieved by the amorphous margin algorithms for a given PTV size. Alternatively, the margin required for a particular level of coverage was always smaller (8–15%) when created with the amorphous algorithms. For the lung cancer patient, the mixed-PDF algorithm resulted in a PTV that was 13% smaller than the clinical PTV while still achieving ≥99.9% coverage. ConclusionsThe amorphous margin algorithms are better suited for the local effects of target shape and positional uncertainties than conventional margins. As a result, they provide superior target coverage with smaller PTVs, ensuring dose delivered to the target while decreasing the risk of normal tissue toxicity.

Planning target volume (PTV) margin practice patterns in adults and paediatrics among the Paediatric Radiation Oncology Society (PROS) members: an international survey

AbstractAimEvolving data are showing the need of considering smaller planning target volume (PTV) margin in paediatrics compared with adults treated for the same body site. This study proposed to evaluate the current patterns of practice regarding the PTV margin in paediatric patients compared with adult patients through an international survey.Materials and methodsA four-item questionnaire was created to address the PTV margins for paediatrics and adults as part of a comprehensive survey. International Paediatric Radiation Oncology Society (PROS) members were selected to partake and were contacted via email.ResultsIn total, 43 responded to the survey. The majority of the responders have written guidelines for PTV margin while the majority of those who have guidelines do not have separate guidelines for paediatrics. The implemented PTV margin for paediatric patients was in the majority 3–5 mm for the head region and 5–10 mm for the torso region and the difference from the PTV margin implemented in adults was not statistically significant.ConclusionThe majority of responders employ a series of site-specific PTV margin protocols that are applied to both adults and paediatrics, and do not take into consideration patient age or size. These results highlight the need of a separate policy for PTV margin in adults and paediatrics in every institution.