Target Volume Margins Research Articles

Development of a Margin Determination Framework for Tumor-Tracking Radiation Therapy With Intraoperatively Implanted Fiducial Markers.

PurposeTo develop an internal target volume (ITV) margin determination framework (or decision-supporting framework) for treating multiple lung metastases using CyberKnife Synchrony with intraoperatively implanted fiducial markers (IIFMs). The feasibility of using non-ideally implanted fiducial markers (a limited number and/or far from a target) for tracking-based lung stereotactic ablative radiotherapy (SABR) was investigated.MethodsIn the developed margin determination framework, an optimal set of IIFMs was determined to minimize a tracking uncertainty-specific ITV (ITVtracking) margin (margin required to cover target-to-marker motion discrepancy), i.e., minimize the motion discrepancies between gross tumor volume (GTV) and the selected set of fiducial markers (FMs). The developed margin determination framework was evaluated in 17 patients with lung metastases. To automatically calculate the respiratory motions of the FMs, a template matching-based FM tracking algorithm was developed, and GTV motion was manually measured. Furthermore, during-treatment motions of the selected FMs were analyzed using log files and compared with those calculated using 4D CTs.ResultsFor 41 of 42 lesions in 17 patients (97.6%), an optimal set of the IIFMs was successfully determined, requiring an ITVtracking margin less than 5 mm. The template matching-based FM tracking algorithm calculated the FM motions with a sub-millimeter accuracy compared with the manual measurements. The patient respiratory motions during treatment were, on average, significantly smaller than those measured at simulation for the patient cohort considered.ConclusionUse of the developed margin determination framework employing CyberKnife Synchrony with a limited number of IIFMs is feasible for lung SABR.

A retrospective comparison of two different immobilization systems for radiotherapy of extremity soft tissue sarcomas and its influence on CTV-PTV margin

BackgroundOn account of extremity wide range of movements and difficulty of reproducibility during irradiation of extremity sarcomas, assorted immobilization strategies are employed to eliminate setup errors. The study purpose was to compare the setup errors of the commonly used immobilization tools and to define planning target volume (PTV) margins for each device.MethodsA retrospective review comparing Vac-Loc™ and thermoplastic cast (Tcast) was conducted. On radiotherapy treatment, portal imaging was matched with the pre-treatment simulation imaging for both fixation tools. The isocenter shifts and total vector error (TVE) were compared. Random (σ) and systemic errors (Σ) were computed and PTV margins were defined.ResultsThree hundred seven shifts in each direction measured in 14 patients. Mean displacements for the Vac-Loc™ and Tcast, respectively, were as follow: vertical; -0.01 cm vs. 0.02 cm, longitudinal; 0.03 cm vs. 0.04; lateral; 0.04 cm vs. 0.00 cm and TVE; 0.15 cm vs. 0.17 cm with no significant statistical difference. Random and systemic errors were comparable for both devices. The lateral displacement and rotational random errors were higher Vac-Loc™ compared to Tcast. Overall measured PTV margins were marginally lower for Tcast compared to Vac-Loc™.ConclusionVac-Loc™ and Tcast are valid options for immobilization with no clear superiority of either device. The marginal advantage of Tcast warrants further prospective studies.

Toward MR-integrated proton therapy: modeling the potential benefits for liver tumors

Magnetic resonance imaging (MRI)-integrated proton therapy (MRiPT) is envisioned to improve treatment quality for many cancer patients. However, given the availability of alternative image-guided strategies, its clinical need is yet to be justified. This study aims to compare the expected clinical outcomes of MRiPT with standard of practice cone-beam CT (CBCT)-guided PT, and other MR-guided methods, i.e. offline MR-guided PT and MR-linac, for treatment of liver tumors. Clinical outcomes were assessed by quantifying the dosimetric and biological impact of target margin reduction enabled by each image-guided approach. Planning target volume (PTV) margins were calculated using random and systematic setup, delineation and motion uncertainties, which were quantified by analyzing longitudinal MRI data for 10 patients with liver tumors. Proton treatment plans were created using appropriate PTV margins for each image-guided PT method. Photon plans with margins equivalent to MRiPT were generated to represent MR-linac. Normal tissue complication probabilities (NTCP) of the uninvolved liver were compared. We found that PTV margin can be reduced by 20% and 40% for offline MR-guided PT and MRiPT, respectively, compared with CBCT-guided PT. Furthermore, clinical target volume expansion could be largely alleviated when delineating on MRI rather than CT. Dosimetric implications included decreased equivalent mean dose of the uninvolved liver, i.e. up to 24.4 Gy and 27.3 Gy for offline MR-guided PT and MRiPT compared to CBCT-guided PT, respectively. Considering Child–Pugh score increase as endpoint, NTCP of the uninvolved liver was significantly decreased for MRiPT compared to CBCT-guided PT (up to 48.4%, p < 0.01), offline MR-guided PT (up to 12.9%, p < 0.01) and MR-linac (up to 30.8%, p < 0.05). Target underdose was possible in the absence of MRI-guidance (D90 reduction up to 4.2 Gy in 20% of cases). In conclusion, MRiPT has the potential to significantly reduce healthy liver toxicities in patients with liver tumors. It is superior to other image-guided techniques currently available.

New fractionations in breast cancer: a dosimetric study of 3D-CRT versus VMAT.

IntroductionAdjuvant radiation therapy (RT) following primary surgery in women affected by early breast cancer (EBC) plays a central role in reducing local recurrences and overall mortality. The FAST‐FORWARD trial recently demonstrated that 1‐week hypofractionated adjuvant RT is not inferior to the standard schedule in terms of local relapse, cosmetic outcomes and toxicity. The aim of this in silico study was to evaluate the dosimetric aspects of a 1‐week RT course, administered through volumetric modulated arc therapy (VMAT), compared with traditional three‐dimensional conformal radiation therapy (3D‐CRT) with tangential fields.MethodsPatients affected by left‐side EBC undergoing adjuvant RT were selected. ESTRO guidelines for the clinical target volume (CTV) delineation and FAST‐FORWARD protocol for CTV to planning target volume (PTV) margin definition were followed. Total prescribed dose was 26 Gy in five fractions. The homogeneity index (HI) and the global conformity index (GCI) were taken into account for planning and dose distribution optimisation purposes. Both 3D‐CRT tangential fields and VMAT plans were generated for each patient.ResultsThe analysis included 21 patients. PTV coverage comparison between 3D‐CRT and VMAT plans showed significant increases for GCI (P < 0.05) in VMAT technique; no statistically significant differences were observed regarding HI. For organs at risks (OAR), statistically significant increases were observed in terms of skin V103% (P < 0.002) and ipsilateral lung V30% (P < 0.05) with 3D‐CRT and of heart V5% (P < 0.05) with VMAT technique.ConclusionsThis in silico study showed that both 3D‐CRT and VMAT are dosimetrically feasible techniques in the framework of 1‐week hypofractionated treatments for left EBC.

782 PATTERNS OF FAILURE AND ADEQUACY OF CLINICAL TARGET VOLUME (CTV) MARGINS IN PATIENTS TREATED WITH DEFINITIVE CHEMO-RADIATION IN ESOPHAGEAL CANCER

Abstract Esophageal cancer is a locally aggressive malignancy with dismal overall survival (OS) rates. Approximately 50–60% of patients fail loco-regionally after definitive chemoradiation (CTRT). There is a lack of consensus regarding clinical target volume (CTV) margins. Improved diagnostic investigations and patterns of failure (POF) data, suggested scope of reduced CTV margins. In this retrospective study, we evaluated the POF (defined as first site of failure) and the adequacy of CTV margins. Methods All patients treated with CTRT between Jan 2013 to Dec 2017 were included. CTV margin was given as 3–5 cm cranio-caudal and 1–1.5 cm radial from gross tumor volume (GTV). Patients were treated either with combined technique (anterior–posterior followed by conformal) or with volumetric arc radiotherapy to a dose of 60-63Gy in 30–35 fractions. PET-CT/CT thorax and upper GI-endoscopy were performed at regular intervals. Loco-regional failure (LRF) was defined as recurrence at local site or regional nodes respectively and classified as infield, marginal and out-field. CT was co-registered with planning CT to document these failures. Results 158 patients were eligible. Twenty-one patients were excluded as they either progressed or did not attend the first follow-up. Median age was 57 years, &amp;gt;90% had squamous histology, and most common subsite was upper third. Median follow-up was 45.8 months, 53 patients (41.7%) had progression. Local recurrence (LR) was seen in 37 (69.8%), followed by regional in 25 (47.1%) and distant in 21 patients (39.6%). All LR were within the GTV. Of regional failures, 50% were within GTV and 50% were outside the radiotherapy portals. This suggest that 3 cm cranio-caudal CTV margin was adequate. Conclusion Our study demonstrated that loco-regional recurrence was the most common pattern of failure after definitive CTRT. As majority of loco-regional failures were within the GTV, hence, 3 cm cranio-caudal CTV margins appear to be adequate enough for control of microscopic disease. Further prospective studies are needed to validate the use of 3 cm CTV margins in definitive CTRT for esophageal cancer.

A novel approach for radiotherapy dose escalation in rectal cancer using online MR-guidance and rectal ultrasound gel filling – Rationale and first in human

IntroductionDose escalated radiotherapy has previously been investigated as a strategy to increase complete response rates in rectal cancer. However large safety margins are required using cone-beam computed tomography guided radiotherapy leading to high doses to organs at risk or insufficient target volume coverage in order to keep dose constraints. We herein present the first clinical application of a new technique for dose escalation in rectal cancer using online magnetic resonance (MR)-guidance and rectal ultrasound gel filling. MethodsA 73-year-old patient with distal cT3a cN0 cM0 rectal cancer was referred for definitive radiochemotherapy with the goal of organ preservation after multidisciplinary discussion. A dose of 45 Gy in 25 fractions with a stereotactic integrated boost to the primary tumor of 50 Gy with concomitant 5-fluorouracil was prescribed. Furthermore, a boost to the primary tumor with 3 Gy per fraction using the adapt-to-shape workflow on a 1.5 T MR-Linac was planned once weekly. For the boost fractions 100 cc of ultrasound gel was applied rectally in order to improve tumor visibility and distancing of uninvolved rectal mucosa. In order to determine the required planning target volume margin diagnostic scans of ten rectal cancer patients conducted with rectal ultrasound gel filling were studied. ResultsBased on the ten diagnostic scans an average isotropic margin of 4 mm was found to be sufficient to cover 95% of the target volume during an online adaptive workflow. Three boost fractions were applied, mean treatment duration was 22:34 min. Treatment was well tolerated by the patient with no more than PRO-CTCAE grade I° toxicity of any kind. The rectal ultrasound gel filling resulted in superior visibility of the tumor and reduced the dose to the involved mucosa especially in the high dose range compared with a boost plan calculated without any filling. A considerable tumor shrinkage was observed during treatment from 17.43 cc at baseline to 4 cc in week four. ConclusionThis novel method appears to be a simple but effective strategy for dose escalated radiotherapy in rectal cancer. Based on the encouraging observation, a prospective trial is currently under preparation.

Effect of abdominal compression on target movement and extension of the external boundary of peripheral lung tumours treated with stereotactic radiotherapy based on four-dimensional computed tomography

BackgroundThis study aimed to investigate the effect of abdominal compression on tumour motion and target volume and to determine suitable planning target volume (PTV) margins for patients treated with lung stereotactic body radiotherapy (SBRT) based on four-dimensional computed tomography (4DCT).MethodsTwenty-three patients diagnosed to have a peripheral pulmonary tumour were selected and divided into an all lesions group (group A), an upper middle lobe lesions group (group B), and a lower lobe lesions group (group C). Two 4DCT scans were performed in each patient, one with and one without abdominal compression. Cone beam computed tomography (CBCT) was performed before starting treatment. The gross target volumes (GTVs) were delineated and internal gross target volumes (IGTVs) were defined. IGTVs were generated using two methods: (1) the maximum intensity projections (MIPs) based on the 4DCT were reconstructed to form a single volume and defined as the IGTVMIP and (2) GTVs from all 10 phases were combined to form a single volume and defined as the IGTV10. A 5-mm, 4-mm, and 3-mm margin was added in all directions on the IGTVMIP and the volume was constructed as PTVMIP5mm, PTVMIP4mm, and PTVMIP3mm.ResultsThere was no significant difference in the amplitude of tumour motion in the left–right, anterior–posterior, or superior-inferior direction according to whether or not abdominal compression was applied (group A, p = 0.43, 0.27, and 0.29, respectively; group B, p = 0.46, 0.15, and 0.45; group C, p = 0.79, 0.86, and 0.37; Wilcoxon test). However, the median IGTVMIP without abdominal compression was 33.67% higher than that with compression (p = 0.00), and the median IGTV10 without compression was 16.08% higher than that with compression (p = 0.00). The median proportion of the degree of inclusion of the IGTVCBCT in PTVMIP5mm, PTVMIP4mm, and PTVMIP3mm ≥ 95% was 100%, 100%, and 83.33%, respectively.ConclusionsAbdominal compression was useful for reducing the size of the IGTVMIP and IGTV10 and for decreasing the PTV margins based on 4DCT. In IGTVMIP with abdominal compression, adding a 4-mm margin to account for respiration is feasible in SBRT based on 4DCT.

Intrafraction stability using full head mask for brain stereotactic radiotherapy.

PurposeWe investigated the immobilization accuracy of a new type of thermoplastic mask—the Double Shell Positioning System (DSPS)—in terms of geometry and dose delivery.MethodsThirty‐one consecutive patients with 1–5 brain metastases treated with stereotactic radiotherapy (SRT) were selected and divided into two groups. Patients were divided into two groups. One group of patients was immobilized by the DSPS (n = 9). Another group of patients was immobilized by a combination of the DSPS and a mouthpiece (n = 22). Patient repositioning was performed with cone beam computed tomography (CBCT) and six‐degree of freedom couch. Additionally, CBCT images were acquired before and after treatment. Registration errors were analyzed with off‐line review. The inter‐ and intrafractional setup errors, and planning target volume (PTV) margin were also calculated. Delivered doses were calculated by shifting the isocenter according to inter‐ and intrafractional setup errors. Dose differences of GTV D99% were compared between planned and delivered doses against the modified PTV margin of 1 mm.ResultsInterfractional setup errors associated with the mouthpiece group were significantly smaller than the translation errors in another group (p = 0.03). Intrafractional setup errors for the two groups were almost the same in all directions. PTV margins were 0.89 mm, 0.75 mm, and 0.90 mm for the DSPS combined with the mouthpiece in lateral, vertical, and longitudinal directions, respectively. Similarly, PTV margins were 1.20 mm, 0.72 mm, and 1.37 mm for the DSPS in the lateral, vertical, and longitudinal directions, respectively. Dose differences between planned and delivered doses were small enough to be within 1% for both groups.ConclusionsThe geometric and dosimetric assessments revealed that the DSPS provides sufficient immobilization accuracy. Higher accuracy can be expected when the immobilization is combined with the use of a mouthpiece.

Does the protocol-required uniform margin around the CTV adequately account for setup inaccuracies in whole breast irradiation?

PurposeTo use cone-beam computed tomography (CBCT) imaging to determine the impacts of patient characteristics on the magnitude of geometric setup errors and obtain patient-specific planning target volume (PTV) margins from the correlated patient characteristics in whole breast irradiation (WBI).MethodsBetween January 2019 and December 2019, a total of 97 patients who underwent breast-conserving surgery, followed by intensity-modulated radiation therapy in WBI, were scanned with pre-treatment CBCT for the first three treatment fractions and weekly for the subsequent fractions. Setup errors in the left–right (LR), superior–inferior (SI) and anterior–posterior (AP) directions were recorded and analyzed with patient characteristics—including age, tumor location, body mass index (BMI), chest circumference (CC) and breast volume (BV)—to examine the predictors for setup errors and obtain specific PTV margins.ResultsA total of 679 CBCT images from 97 patients were acquired for analysis. The mean setup errors for the whole group were 2.32 ± 1.21 mm, 3.71 ± 2.21 mm and 2.75 ± 1.56 mm in the LR, SI and AP directions, respectively. Patients’ BMI, CC and BV were moderately associated with setup errors, especially in the SI directions (R = 0.40, 0.43 and 0.22, respectively). Setup errors in the SI directions for patients with BMI > 23.8 kg/m2, CC > 89 cm and BV > 657 cm3 were 4.56 ± 2.59 mm, 4.77 ± 2.42 mm and 4.30 ± 2.43 mm, respectively, which were significantly greater than those of patients with BMI ≤ 23.8 kg/m2, CC ≤ 89 cm and BV ≤ 657 cm3 (P < 0.05). Correspondingly, the calculated PTV margins in patients with BMI > 23.8 kg/m2, CC > 89 cm and BV > 657 cm3 were 4.25/7.95/4.93 mm, 4.37/7.66/5.24 mm and 4.22/7.54/5.29 mm in the LR/SI/AP directions, respectively, compared with 3.64/4.64/5.09 mm, 3.31/4.50/4.82 mm and 3.29/5.74/4.73 mm for BMI ≤ 23.8 kg/m2, CC ≤ 89 cm and BV ≤ 657 cm3, respectively.ConclusionsThe magnitude of geometric setup errors was moderately correlated with BMI, CC and BV. It was recommended to set patient-specific PTV margins according to patient characteristics in the absence of daily image-guided treatment setup.

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.

Planning target volume margin assessment for online adaptive MR-guided dose-escalation in rectal cancer on a 1.5 T MR-Linac

PurposeThis study assessed the margins needed to cover tumor intrafraction motion during an MR-guided radiotherapy (MRgRT) dose-escalation strategy in intermediate risk rectal cancer. MethodsFifteen patients with rectal cancer were treated with neoadjuvant short-course radiotherapy, 5x5 Gy, according to an online adaptive workflow on a 1.5 T MR-linac. Per patient, 26 3D T2 weighted MRIs were made; one reference scan preceding treatment and five scans per treatment fraction. The primary tumor was delineated on each scan as gross tumor volume (GTV). Target coverage margins were assessed by isotropically expanding the reference GTV until more than 95% of the voxels of the sequential GTVs were covered. A margin with a coverage probability threshold of 90% was defined as adequate. Intra- and interfraction margins to cope with the movement of the GTV in the period between scans were calculated to indicate the target volume margins. Furthermore, the margin needed to cover GTV movement was calculated for different time intervals. ResultsThe required margins to cover inter- and intrafraction GTV motion were 17 mm and 6 mm, respectively. Analysis based on time intervals between scans showed smaller margins were needed for adequate GTV coverage as time intervals became shorter, with a 4 mm margin required for a procedure of 15 min or less. ConclusionThe shorter the treatment time, the smaller the margins needed to cover for the GTV movement during an online adaptive MRgRT dose-escalation strategy for intermediate risk rectal cancer. When time intervals between replanning and the end of dose delivery could be reduced to 15 min, a 4 mm margin would allow adequate target coverage.

Moving Unfavorable Small-Bowel Anatomy Away From the Prostate to Optimize Radiation Therapy Plans With the GU-Lok

Patients with localized prostate cancer comprise a large volume of treatments in radiation therapy centers. Occasionally, individual patient anatomy makes the safe delivery of an effective dose of radiation therapy challenging. We describe 2 cases of patients with a small bowel deep in the pelvis within the planning target volume with subsequent suboptimal radiation therapy treatment plans. We explore how we used the GU-Lok, a prostate immobilization device, to move the small bowel away from the prostate, and tighten target volume margins to help facilitate safe and effective treatment.

Evidence-Based Planning Target Volume Margin Reduction for Modern Lung Stereotactic Ablative Radiation Therapy Using Deformable Registration

PurposeStandard planning target volume (PTV) margins for lung stereotactic ablative radiation therapy (SABR) are 5 mm. High-dose-rate volumetric modulated arc therapy delivered using flattening filter-free (FFF) beams with modern immobilization systems may allow for PTV margin reduction. This study assesses whether PTV margins can be reduced from 5 to 3 mm. MethodsTarget intrafractional motions derived from pretreatment and posttreatment cone beam computed tomography (CBCT) scans for 33 patients receiving lung SABR treated with 10XFFF energy and 5-mm PTV margins from 2016 to 2019 were used to calculate the required PTV margin. Deformable registration of the planning CT scan and internal gross tumor volume (IGTV) contour to posttreatment CBCT scans for 36 consecutive patients with 4 fraction schedules was completed to capture volume changes and intrafractional movement. Plans were replanned with 3-mm margins and recalculated on each deformed CT scan to assess deformed IGTV (d-IGTV) coverage and organ-at-risk doses. ResultsMargin analysis showed PTV margins may be reduced to 3 mm. The mean d-IGTV coverage (percentage of the d-IGTV receiving ≥100% of the prescription dose [V100%] and the minimum dose covering 99.9% of the d-IGTV volume [D99.9%]) over 4 fractions for each patient was >95% with both margins. With 5-mm PTV margins, all 144 fractions had a d-IGTV V100% of >95% and a D99.9% >95%. With 3-mm PTV margins, the d-IGTV V100% was >95% in 99.3% of fractions (143 of 144) and the D99.9% was >95% in 98.6% of fractions (142 of 144). With 3-mm PTV margins, significant reductions in body V50%, body V80%, the volume of the lung receiving ≥20 Gy, and the mean lung dose and chest wall dose to 0.035 cm3 and 30 cm3 were observed (all P < .001). Using theoretical models, the normal tissue complication probability for radiation pneumonitis decreased by a mean of 0.8% (range, 0.1%-2.7%), and the mean 2-year tumor control probability was 96.1% and 95.2% with 5-mm and 3-mm PTV margins, respectively. ConclusionWith modern treatment and immobilization techniques in lung SABR, 3-mm PTV margins maintain acceptable IGTV coverage, modestly reduce toxicity to organs at risk, and maintain a calculated 2-year local control rate of >95%.

Mesorectal shape variation in rectal cancer radiotherapy in prone position using a belly board.

In rectal cancer patients, radiotherapy in prone position using a belly board can reduce the dose to organs at risk. For this patient group we investigated inter-fraction shape variation of the mesorectal part of the clinical target volume (CTV) and determined planning target volume (PTV) margins. Patients with rectal cancer receiving neoadjuvant (chemo)radiotherapy were eligible. For each patient a planning computed tomography (pCT) and five cone-beam CT (CBCT) scans were acquired in prone position using a belly board. The mesorectal CTV was delineated on all scans. Mesorectal shape variation was quantified relative to the pCT. PTV margins were derived locally and averaged for separate subregions of the mesorectal CTV. For each patient a total PTV was constructed using our clinical margins for mesorectal and lymph node CTVs. An artificial dose distribution conforming to this PTV was used to calculate the coverage for the mesorectal CTV using the CBCT delineations. In 19 rectal cancer patients the derived PTV margins were smallest in the upper-lateral region (6mm) and largest in the upper-anterior region (16mm). PTV margins for the upper-anterior region were larger for female patients (19mm) compared to male patients (14mm). Clinical margins for the total PTV were sufficient for a coverage of at least 97% of the mesorectal CTV for all patients. Mesorectal shape variation is heterogeneous and largest in the upper-anterior region, in rectal cancer patients irradiated in prone position and using a belly board.

CyberKnife radiation therapy as a platform for translational mouse studies

Purpose Radiation therapy (RT) is a common nonsurgical treatment in the management of patients with cancer. While genetically engineered mouse models (GEMM) recapitulate human disease, conventional linear particle accelerator systems are not suited for state-of-the-art, imageguided targeted RT (IGRT) of these murine tumors. We employed the CyberKnife (CK; Accuray) platform for IGRT of GEMM-derived non-small cell lung cancer (NSCLC) lesions. Material and methods GEMM-derived KrasLSL-G12D/+/Trp53fl/fl -driven NSCLC flank tumors were irradiated using the CK RT platform. We applied IGRT of 2, 4, 6, and 8 Gy using field sizes of 5–12.5 mm to average gross tumor volumes (GTV) of 0.9 cm3 using Xsight Spine Tracking (Accuray). Results We found that 0 mm planning target volume (PTV) margin is sufficient for IGRT of murine tumors using the CK. We observed that higher RT doses (6–8 Gy) decreased absolute cell numbers of tumor infiltrating leukocytes (TIL) by approximately half compared to low doses (2–4 Gy) within 1 h, but even with low dose RT (2 Gy) TIL were found to be reduced after 8–24 h. Conclusion We here demonstrate that the CK RT system allows for targeted IGRT of murine tumors with high precision and constitutes a novel promising platform for translational mouse RT studies.

Performance stability evaluation of atlas-based machine learning radiation therapy treatment planning in prostate cancer

Atlas-based machine learning (ML) for radiation therapy (RT) treatment planning is effective at tailoring dose distributions to account for unique patient anatomies by selecting the most appropriate patients from the training database (atlases) to inform dose prediction for new patients. However, variations in clinical practice between the training dataset and a new patient to be planned may impact ML performance by confounding atlas selection. In this study, we simulated various contouring practices in prostate cancer RT to investigate the impact of changing input data on atlas-based ML treatment planning. We generated 225 ML plans for nine bespoke contouring protocol scenarios (reduced target margins, modified organ-at-risk (OAR) definitions, and inclusion of optional OARs less represented in the training database) on 25 patient datasets by applying a single, previously trained and validated ML model for prostate cancer followed by dose mimicking to create a final deliverable plan. ML treatment plans for each scenario were compared to base ML treatment plans that followed a contouring protocol consistent with the model training data. ML performance was evaluated based on atlas distance metrics that are calculated during ML dose prediction. There were significant changes between atlases selected for the base ML treatment plans and treatment plans when planning target volume margins were reduced and/or optional OARs were included. The deliverability of ML predicted dose distributions based on gamma analysis between predicted and mimicked final deliverable dose showed significant differences for seven out of eight scenarios compared with the base ML treatment plans. Overall, there were small but statistically significant dosimetric changes in predicted and mimicked dose with addition of optional OAR contours. This work presents a framework for benchmarking and performance monitoring of ML treatment planning algorithms in the context of evolving clinical practices.

Organ motion in linac-based SBRT for glottic cancer

PurposeThe purpose of this study is to evaluate inter- and intra-fraction organ motion as well as to quantify clinical target volume (CTV) to planning target volume (PTV) margins to be adopted in the stereotactic treatment of early stage glottic cancer.Methods and materialsStereotactic body radiotherapy (SBRT) to 36 Gy in 3 fractions was administered to 23 patients with early glottic cancer T1N0M0. Patients were irradiated with a volumetric intensity modulated arc technique delivered with 6 MV FFF energy. Each patient underwent a pre-treatment cone beam computed tomography (CBCT) to correct the setup based on the thyroid cartilage position. Imaging was repeated if displacement exceeded 2 mm in any direction. CBCT imaging was also performed after each treatment arc as well as at the end of the delivery. Swallowing was allowed only during the beam-off time between arcs. CBCT images were reviewed to evaluate inter- and intra-fraction organ motion. The relationships between selected treatment characteristics, both beam-on and delivery times as well as organ motion were investigated.ResultsFor the population systematic (Ʃ) and random (σ) inter-fraction errors were 0.9, 1.3 and 0.6 mm and 1.1, 1.3 and 0.7 mm in the left-right (X), cranio-caudal (Y) and antero-posterior (Z) directions, respectively. From the analysis of CBCT images acquired after treatment, systematic (Ʃ) and random (σ) intra-fraction errors resulted 0.7, 1.6 and 0.7 mm and 1.0, 1.5 and 0.6 mm in the X, Y and Z directions, respectively. Margins calculated from the intra-fraction errors were 2.4, 5.1 and 2.2 mm in the X, Y and Z directions respectively. A statistically significant difference was found for the displacement in the Z direction between patients irradiated with > 2 arcs versus ≤ 2 arcs, (MW test, p = 0.038). When analyzing mean data from CBCT images for the whole treatment, a significant correlation was found between the time of delivery and the three dimensional displacement vector (r = 0.489, p = 0.055), the displacement in the Y direction (r = 0.553, p = 0.026) and the subsequent margins to be adopted (r = 0.626, p = 0.009). Finally, displacements and the subsequent margins to be adopted in Y direction were significantly greater for treatments with more than 2 arcs (MW test p = 0.037 and p = 0.019, respectively).ConclusionsIn the setting of controlled swallowing during treatment delivery, intra-fraction motion still needs to be taken into account when planning with estimated CTV to PTV margins of 3, 5 and 3 mm in the X, Y and Z directions, respectively. Selected treatments may require additional margins.

Size and Predictive Factors of Microscopic Tumor Extension in Locally Advanced Non-Small Cell Lung Cancer

PurposeRadiation therapy for locally advanced non-small cell lung cancer (NSCLC) should treat the whole tumor, including its microscopic extensions, and protect adjacent organs at risk as much as possible. The aim of our study is to evaluate the size of microscopic tumor extension (MEmax) in NSCLC, and search for potential predictive factors. Methods and MaterialsWe retrospectively selected 70 patients treated with postoperative radiation therapy for a NSCLC with N2 nodal status, then 34 additional patients operated for a squamous cell lung cancer with N1 or N2 nodal status. On the digitized slides originating from the resected tumors of these 104 patients, we outlined the border of the tumor, as seen with the naked eye. We then searched for microscopic tumor extension outside of these borders with a magnification as high as 40 × and measured the maximum size of MEmax. ResultsThe median MEmax in the whole cohort was 0.85 mm (0-9.95). The MEmax was <5.3 mm in 95% of adenocarcinomas (6.5 mm in the subgroup without neoadjuvant chemotherapy) and <3.5 mm in 95% of squamous cell carcinomas (3.7 mm in the subgroup without neoadjuvant chemotherapy). After multivariate analysis, the factors associated with the size of MEmax were vascular invasion (P = .0002), histologic type, with a wider MEmax for adenocarcinomas in comparison with squamous cell carcinomas (P = .002), tumor size, which was inversely related with the size of MEmax (P = .024), and high blood pressure (P = .03). Macroscopic histologic tumor size was well correlated with both radiologic tumor size on a mediastinal setting computed tomography (correlation coefficient of 0.845) and on a parenchymal setting computed tomography (correlation coefficient of 0.836). ConclusionsThe clinical target volume margin, accounting for microscopic tumoral extension, could be reduced to 7 mm for adenocarcinomas and 4 mm for squamous cell carcinomas.

Automated algorithm for calculation of setup corrections and planning target volume margins for offline image-guided radiotherapy protocols.

PurposeEach radiotherapy center should have a site‐specific planning target volume (PTV) margins and image‐guided (IG) radiotherapy (IGRT) correction protocols to compensate for the geometric errors that can occur during treatment. This study developed an automated algorithm for the calculation and evaluation of these parameters from cone beam computed tomography (CBCT)‐based IG‐intensity modulated radiotherapy (IG‐IMRT) treatment.Methods and materialsA MATLAB algorithm was developed to extract the setup errors in three translational directions (x, y, and z) from the data logged by the CBCT system during treatment delivery. The algorithm also calculates the resulted population setup error and PTV margin based on the van Herk margin recipe and subsequently estimates their respective values for no action level (NAL) and extended no action level (eNAL) offline correction protocols. The algorithm was tested on 25 head and neck cancer (HNC) patients treated using IG‐IMRT.ResultsThe algorithms calculated that the HNC patients require a PTV margin of 3.1, 2.7, and 3.2 mm in the x‐, y‐, and z‐direction, respectively, without IGRT. The margin can be reduced to 2.0, 2.2, and 3.0 mm in the x‐, y‐, and z‐direction, respectively, with NAL and 1.6, 1.7, and 2.2 mm in the x‐, y‐, and z‐direction, respectively, with eNAL protocol. The results obtained were verified to be the same with the margins calculated using an Excel spreadsheet. The algorithm calculates the weekly offline setup error correction values automatically and reduces the risk of input data error observed in the spreadsheet.ConclusionsIn conclusion, the algorithm provides an automated method for optimization and reduction of PTV margin using logged setup errors from CBCT‐based IGRT.

Determining optimal clinical target volume margins in high-grade glioma based on microscopic tumor extension and magnetic resonance imaging

IntroductionIn this study, we performed a consecutive macropathologic analysis to assess microscopic extension (ME) in high-grade glioma (HGG) to determine appropriate clinical target volume (CTV) margins for radiotherapy.Materials and methodsThe study included HGG patients with tumors located in non-functional areas, and supratotal resection was performed. The ME distance from the edge of the tumor to the microscopic tumor cells surrounding brain tissue was measured. Associations between the extent of ME and clinicopathological characteristics were evaluated by multivariate linear regression (MVLR) analysis. An ME predictive model was developed based on the MVLR model.ResultsBetween June 2017 and July 2019, 652 pathologic slides obtained from 30 HGG patients were analyzed. The mean ME distance was 1.70 cm (range, 0.63 to 2.87 cm). The MVLR analysis identified that pathologic grade, subventricular zone (SVZ) contact and O6-methylguanine-DNA methyltransferase (MGMT) methylation, isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion status were independent variables predicting ME (all P < 0.05). A multivariable prediction model was developed as follows: YME = 0.672 + 0.513XGrade + 0.380XSVZ + 0.439XMGMT + 0.320XIDH + 0.333X1p/19q. The R-square value of goodness of fit was 0.780. The receiver operating characteristic curve proved that the area under the curve was 0.964 (P < 0.001).ConclusionME was heterogeneously distributed across different grades of gliomas according to the tumor location and molecular marker status, which indicated that CTV delineation should be individualized. The model could predict the ME of HGG, which may help clinicians determine the CTV for individual patients.Trial registration The trial was registered with Chinese Clinical Trial Registry (ChiCTR2100046106). Registered 4 May 2021-Retrospectively registered.