Mean Gross Tumor Volume Research Articles

Single institution experience of MRI-guided radiotherapy for thoracic tumors and clinical characteristics impacting treatment duty cycle.

MRI-guided radiotherapy (MRgRT) allows for direct motion management and real-time radiation treatment plan adaptation. We report our institutional experience using low strength 0.35T MRgRT for thoracic malignancies, and evaluate changes in treatment duty cycle between first and final MRgRT fractions. All patients with intrathoracic tumors treated with MRgRT were included. The primary reason for MRgRT (adjacent organ at risk [OAR] vs. motion management [MM] vs. other) was recorded. Tumor location was classified as central (within 2cm of tracheobronchial tree) vs. non-central, and further classified by the Expanded HILUS grouping. Gross tumor volume (GTV) motion, planning target volume expansions, dose/fractionation, treatment plan time, and total delivery time were extracted from the treatment planning system. Treatment plan time was defined as the time for beam delivery, including multileaf collimator (MLC) motion, and gantry rotation. Treatment delivery time was defined as the time from beam on to completion of treatment, including treatment plan time and patient respiratory breath holds. Duty cycle was calculated as treatment plan time/treatment delivery time. Duty cycles were compared between first and final fraction using a two-sample t-test. Twenty-seven patients with thoracic tumors (16 non-small cell lung cancer and 11 thoracic metastases) were treated with MRgRT between 12/2021 and 06/2023. Fifteen patients received MRgRT due to OAR and 11 patients received MRgRT for motion management. 11 patients had central tumors and all were treated with MRgRT due to OAR risk. The median dose/fractionation was 50 Gy/5 fractions. For patients treated due to OAR (n=15), 80% had at least 1 adapted fraction during their course of radiotherapy. There was no plan adaptation for patients treated due to motion management (n=11). Mean GTV motion was significantly higher for patients treated due to motion management compared to OAR (16.1mm vs. 6.5mm, p=0.011). Mean duty cycle for fraction 1 was 54.2% compared to 62.1% with final fraction (p=0.004). Mean fraction 1 duty cycle was higher for patients treated due to OAR compared to patients treated for MM (61% vs. 45.0%, p=0.012). Duty cycle improved from first fraction to final fraction possibly due to patient familiarity with treatment. Duty cycle was improved for patients treated due to OAR risk, likely due to more central location and thus decreased target motion.

Efficacy and safety of FDG-PET for determining target volume during intensity-modulated radiotherapy for head and neck cancer involving the oral level

PurposeTo determine the efficacy and safety of target volume determination by 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) for intensity-modulated radiation therapy (IMRT) for locally advanced head and neck squamous cell carcinoma (HNSCC) extending into the oral cavity or oropharynx.MethodsWe prospectively treated 10 consecutive consenting patients with HNSCC using IMRT, with target volumes determined by PET-CT. Gross tumor volume (GTV) and clinical target volume (CTV) at the oral level were determined by two radiation oncologists for CT, magnetic resonance imaging (MRI), and PET-CT. Differences in target volume (GTVPET, GTVCT, GTVMRI, CTVPET, CTVCT, and CTVMRI) for each modality and the interobserver variability of the target volume were evaluated using the Dice similarity coefficient and Hausdorff distance. Clinical outcomes, including acute adverse events (AEs) and local control were evaluated.ResultsThe mean GTV was smallest for GTVPET, followed by GTVCT and GTVMRI. There was a significant difference between GTVPET and GTVMRI, but not between the other two groups. The interobserver variability of target volume with PET-CT was significantly less than that with CT or MRI for GTV and tended to be less for CTV, but there was no significant difference in CTV between the modalities. Grade ≤ 3 acute dermatitis, mucositis, and dysphagia occurred in 55%, 88%, and 22% of patients, respectively, but no grade 4 AEs were observed. There was no local recurrence at the oral level after a median follow-up period of 37 months (range, 15–55 months).ConclusionsThe results suggest that the target volume determined by PET-CT could safely reduce GTV size and interobserver variability in patients with locally advanced HNSCC extending into the oral cavity or oropharynx undergoing IMRT.Trial registrationUMIN, UMIN000033007. Registered 16 jun 2018, https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000037631

Volumetric MRI with sparse sampling for MR-guided 3D motion tracking via sparse prior-augmented implicit neural representation learning.

Volumetric reconstruction of magnetic resonance imaging (MRI) from sparse samples is desirable for 3D motion tracking and promises to improve magnetic resonance (MR)-guided radiation treatment precision. Data-driven sparse MRI reconstruction, however, requires large-scale training datasets for prior learning, which is time-consuming and challenging to acquire in clinical settings. To investigate volumetric reconstruction of MRI from sparse samples of two orthogonal slices aided by sparse priors of two static 3D MRI through implicit neural representation (NeRP) learning, in support of 3D motion tracking during MR-guided radiotherapy. A multi-layer perceptron network was trained to parameterize the NeRP model of a patient-specific MRI dataset, where the network takes 4D data coordinates of voxel locations and motion states as inputs and outputs corresponding voxel intensities. By first training the network to learn the NeRP of two static 3D MRI with different breathing motion states, prior information of patient breathing motion was embedded into network weights through optimization. The prior information was then augmented from two motion states to 31 motion states by querying the optimized network at interpolated and extrapolated motion state coordinates. Starting from the prior-augmented NeRP model as an initialization point, we further trained the network to fit sparse samples of two orthogonal MRI slices and the final volumetric reconstruction was obtained by querying the trained network at 3D spatial locations. We evaluated the proposed method using 5-min volumetric MRI time series with 340ms temporal resolution for seven abdominal patients with hepatocellular carcinoma, acquired using golden-angle radial MRI sequence and reconstructed through retrospective sorting. Two volumetric MRI with inhale and exhale states respectively were selected from the first 30s of the time series for prior embedding and augmentation. The remaining 4.5-min time series was used for volumetric reconstruction evaluation, where we retrospectively subsampled each MRI to two orthogonal slices and compared model-reconstructed images to ground truth images in terms of image quality and the capability of supporting 3D target motion tracking. Across the seven patients evaluated, the peak signal-to-noise-ratio between model-reconstructed and ground truth MR images was 38.02±2.60dB and the structure similarity index measure was 0.98±0.01. Throughout the 4.5-min time period, gross tumor volume (GTV) motion estimated by deforming a reference state MRI to model-reconstructed and ground truth MRI showed good consistency. The 95-percentile Hausdorff distance between GTV contours was 2.41±0.77mm, which is less than the voxel dimension. The mean GTV centroid position difference between ground truth and model estimation was less than 1mm in all three orthogonal directions. A prior-augmented NeRP model has been developed to reconstruct volumetric MRI from sparse samples of orthogonal cine slices. Only one exhale and one inhale 3D MRI were needed to train the model to learn prior information of patient breathing motion for sparse image reconstruction. The proposed model has the potential of supporting 3D motion tracking during MR-guided radiotherapy for improved treatment precision and promises a major simplification of the workflow by eliminating the need for large-scale training datasets.

Use of Lattice Therapy for Dose-Escalation in Palliative Treatment of Bulky Head and Neck Tumors

Palliative radiation is used to relieve pain and bleeding in patients with locally advanced head and neck cancers. Lower doses are utilized to meet normal tissue tolerances, limiting the duration of palliation. Lattice therapy can achieve intratumoral dose escalation while sparing surrounding tissues, but a standard approach does not exist. In this study, we explore the impact of variation in the values and distributions of peak and valley doses in palliative lattice treatment plans. Five-fraction volumetric-arc based (VMAT) lattice plans were generated using a customized Python v3.6 script. For each combination of peak/valley doses and sphere size and spacing, a bounding box was generated around the gross tumor volume (GTV) and divided into equal segments in the x, y, and z planes. Individual spheres were constructed for a given parameter set and those fully encompassed within the target contracted by 2 cm were used to create peak dose targets with values of 30, 40, and 50 Gy. A valley dose of 20 Gy was chosen to match standard dosing for 5-fraction palliative plans and the associated target volumes were generated by subtracting an 8 mm expansion of the peak dose spheres from the overall target volume. Multi-criteria optimization (MCO) was used to generate a final plan. The planning target volume (PTV) was a uniform 3-mm expansion from the GTV. Target volume and OAR dosimetric parameters were analyzed using Mann-Whitney U and Kruskal-Wallis testing. A total of 72 unique plans were evaluated for 4 patients with large GTV sizes ranging from 159 to 413 cm3. The median time to generate an individual plan using the automated script was 20 minutes (IQR, 18 - 23). Median values of mean GTV and PTV doses were 27.9 Gy (IQR, 24.7 - 30.3) and 26.7 Gy (IQR, 23.9 - 29.1), respectively. Further analysis was then limited to plans containing ablative 50 Gy dose spheres. For these 24 plans, mean GTV and PTV doses increased to a median of 31.7 Gy (IQR, 29.6 - 33.3) and 29.6 Gy (IQR, 27.8 - 31.0), respectively. Mean doses to 1, 2, and 4 cm expansions around the GTV for this cohort had median values of 19.5 Gy, 15.1 Gy, and 9.7 Gy, respectively. Median doses to 0.03 cc of mandible, spinal cord, and esophagus were 28.2 Gy (range, 7.0 - 35.7), 14.7 Gy (range, 9.8 - 18.8), and 8.7 Gy (range, 0.8 - 16.2), respectively. Mean GTV dose was dependent on sphere spacing (median 29.9 Gy for 4 cm spacing vs. 33.5 Gy for 3 cm, p<0.001), but not on sphere size (median 31.3 Gy for 2 cm vs. 31.8 Gy for 1.5 cm vs. 31.5 Gy for 1 cm, p = 0.968). VMAT-based lattice planning allows dose escalation to bulky head and neck tumors, including significant coverage with ablative doses while meeting normal tissue constraints. Thus, lattice plans could enhance palliation while reducing toxicity. Mean target coverage is dependent on sphere spacing. Use of automated plan generation could also facilitate clinical application.

Feasibility and Safety of Single-Isocenter/Multi-Lesion (SIML) HyperArc Brain SRT: Clinical Implementation and Early Outcomes

Patients with multiple brain metastases may not tolerate relatively longer treatment times for traditional stereotactic radiation therapy (SRT) with individual isocenter plans for each lesion due to discomfort or co-morbidities. SRT using a single-isocenter/multi-lesion (SIML) HyperArc volumetric modulated arc therapy (VMAT) plan with flattening filter free (FFF) beam could significantly shorten overall treatment time, and improve patient comfort, compliance, and clinic efficiency. We report early clinical results of treating multiple brain metastases with SIML HyperArc SRT. Twenty-three patients with multiple brain metastatic tumors (range, 2-9 lesions; total treated lesions, n = 96) were simulated using Encompass support and Q-fix mask, and treated with a highly-conformal SIML VMAT SRT plans via non-coplanar HyperArc geometry. Mean tumor distance to isocenter was 5.3 cm, maximum up to 7 cm. Common prescriptions were 25-30 Gy/5 fractions, 24-27 Gy/3 fractions, and 20 Gy/1 fraction prescribed to each planning target volume (PTV) using 2 mm margin around standard gross tumor volume (GTV) delineated on contrasted enhanced MP-RAGE MRI fusion. Acuros dose calculation for 6MV-FFF beam was used for tissue heterogeneity corrections. Alliance A071801 criteria was used for dose constraints to organs at risk (OAR) and target conformality. Treatment was delivered every other day with CBCT-guidance, adjustments made with 6DOF couch corrections on a medical linear accelerator, and treatment delivery time within 15 minutes. Local control rates were reported, and toxicity profile rated based on CTCAE v5.0 for brain radionecrosis, optic neuropathy, and brainstem dysfunction. All plans met Alliance A071801 requirements for each tumor coverage, dose to OAR including optic apparatus, brainstem, and spinal cord. Mean GTV and PTV volume were 9.4 cc (range, 0.3-54.8 cc) and 16.13 cc (range, 1.0-80.2 cc). Patient-specific quality assurance results were 98.3% for gamma passing criteria of 2%/2mm. Independent in-house Monte Carlo physics second check agreed with HyperArc plans by ±3.0%. Mean follow up was 6 months (range, 0.0-18.6 months). Of the 23 patients treated, 17 (74%) had post-treatment MRI imaging to assess local control and toxicity. Local control was achieved in 69/73 (95%) of treated and followed lesions. CTCAE grade 2 radionecrosis occurred in 2 patients and were managed with dexamethasone. No CTCAE grade 3+ events of radionecrosis, optic pathway dysfunction, or brainstem toxicity were observed. SIML HyperArc Brain SRT for multiple brain metastases has excellent local control and low toxicity profile in our patients. It can significantly reduce treatment delivery time as compared to traditional multiple-isocenter brain SRT or chronologically separate treatment courses and thus, help to improve patient comfort, compliance, ease of care, and clinic workflow. Longer median follow up of SIML brain SRT on larger patient cohort is warranted.

Preoperative Radiotherapy of Soft Tissue Sarcoma with Simultaneous Integrated Boost: A Phase II Study

Neoadjuvant radiotherapy to 50 Gy in 25 fractions is delivered in operable Soft Tissue Sarcoma (STS) patients to downstage the tumor and improve resectability, although at the expense of increased risk of wound dehiscence. Nonetheless, clear margin resection (R0) may not be achieved in tumors located in proximity of critical structures such as the neurovascular bundle (NVB), resulting in impaired local control. The aim of this study is to increase R0 rate through addition of an IMRT boost to the potential sites of suboptimal resection in STS patients receiving neoadjuvant RT. We report hereby the dosimetric results and safety results from the first 5 patients enrolled in this trial. We designed a prospective monocentric interventional single-arm Phase II study enrolling locally advanced STS eligible for surgery. RT is administered in 25 daily fractions to include the MRI-based Gross Tumor Volume (GTV) and peritumoral tissue at risk of microscopic spread (CTV1) to a dose of 50 Gy (2Gy/fraction), with SIB (Simultaneous Integrated Boost) intensification to the tumor/dissection plane interface (CTV2) to a dose of 60 Gy (2.4 Gy/fraction). CTV2 delineation is approved by both a Radiation Oncologist and Surgeon. A margin of 0.5 cm is applied to both CTV to obtain PTV1 and PTV2. Concurrent anthracyclines-based chemotherapy (ChT) is allowed up to 3 cycles. Primary endpoint is R0 resection rate. Secondary endpoints include pathologic complete response rate, objective response rate, overall survival, local and distant progression-free survival, acute and chronic toxicity rate. To assess an increase in R0 rate from 81% to 97% assuming β = 80% e α = 0.05, 33 patients will be included. Dose constraints are summarized in Table1. At least 95% of the PTV1 and PTV2 should be covered by 95% the prescription dose up to a maximum allowed dose of 107%. Five patients were included. Tumor was located in the limbs and in the trunk in respectively 4 and 1 patient. Mean age was 47 years (range: 19-67). Concurrent chemotherapy was performed in 2 patients. Mean GTV size was 228.6 cm3 (range: 59.8-314.5). Mean PTV coverage by the 95% of the dose prescription was 98% (95-100) and 97% (95-100) in PTV1 and PTV2, respectively. Mean PTV1 and PTV2 Dmax were 61.6 Gy (range: 59-63) and 64.1 Gy (range:63-66), in both cases below the 107% threshold. Mean Bone Dmax was 55 Gy (56.6-61.8 Gy). Dmax to the skin corridor exceeded 20 Gy in 1 patient (range 12.5-58.1). While the NVB was overlapping the PTV2 in all cases, Dmax was below 66 Gy. At the time of this report, no Grade ≥3 acute skin toxicity was observed. Two patients underwent surgery with a radiological partial response (RECIST) and pathological complete response. No major wound complication was reported. Planning goals of the first 5 enrolled patients are achieved in most cases. Preliminary results show a benign safety profile and promising tumor response rate.

Outcomes of 30 Gy/5 Fr Hypofractionated Stereotactic Radiation Therapy for Small Brain Metastases (≤2 cm).

Stereotactic radiosurgery (SRS)-used for brain metastases (BMs) with a tumor diameter of ≤2 cm-has a high local control rate, however, it can cause symptomatic radiation-induced brain necrosis. Hypofractionated stereotactic radiation therapy (HFSRT) is not commonly used for such lesions and its effectiveness remains unknown. Herein, the efficacy of 30 Gy 5-fraction HFSRT for treating BMs of <2 cm was retrospectively evaluated. Patients who received HFSRT and had a gross tumor volume (GTV) of ≤2 cm in maximum diameter were included in the study (49 patients; 179 BMs; median follow-up period, 11.9 months). The mean GTV Peripheral Dose (D95) was 36.2 Gy. The local control (LC) rates at 1 and 2 years were 93.0% and 81.5%, respectively, for all lesions. The 1-year LC rates were 93.6% and 92.0% for ≤1.0-cm and 1.0-2.0-cm lesions, respectively. Multivariate analysis revealed that the only significant difference was in GTV maximal tumor diameter (HR=1.961, p=0.0002). Notably, only one patient had asymptomatic radiation necrosis. Owing to the high toxicity of SRS, 5-fraction HFSRT can be an effective treatment strategy for BMs of <2 cm.

Real Time Volumetric MRI for MR-Guided 3D Motion Tracking via Sparse Prior-Augmented Neural Representation Learning

To reconstruct volumetric MRI from orthogonal cine acquisition aided by sparse priors of 2 static 3D MRI through implicit neural representation (NeRP) learning, with the goal of eliminating large-scale training datasets for data-driven sparse MRI reconstruction and supporting clinical workflow of real time 3D motion tracking during MR-guided radiotherapy. A multi-layer perceptron network was trained to learn the NeRP of a patient-specific MRI dataset, where the network takes 4D data coordinates of voxel locations and motion states as inputs and outputs corresponding voxel intensities. By first learning the NeRP of 2 static 3D MRI with different breathing motion states, prior knowledge of patient breathing motion was embedded into network weights through optimization. The prior knowledge was then augmented from 2 to 31 motion states by querying the optimized network at interpolated/extrapolated motion state coordinates. Starting from the prior-augmented network as an initialization point, the network was further trained using sparse samples of 2 orthogonal cine slices. The final volumetric reconstruction was obtained by querying the trained network at desired 3D spatial locations. We evaluated the proposed method using 5-minute volumetric MRI time series with 340 ms temporal resolution collected from 7 liver carcinoma patients. The time series was acquired using golden-angle radial MRI sequence and reconstructed through retrospective sorting. Two MRI with inhale and exhale states respectively were selected from the first 30 sec of the time series for prior embedding and augmentation. The remaining 4.5-min time series was used for volumetric reconstruction evaluation, where we retrospectively subsampled each MRI to 2 orthogonal slices and compared network-reconstructed images to ground truth images in terms of image quality and the capability of supporting 3D target motion tracking. Across the 7 patients evaluated, the peak signal to noise ratio between model reconstruction and ground truth was 54.66 ± 6.16 dB and the structural similarity index measure was 0.99 ± 0.01. Gross tumor volume (GTV) contours estimated by deforming a reference state MRI to model-reconstructed and ground truth MRI showed good consistency. The 95-percentile Hausdorff distance between GTV contours was 1.89 ± 1.13 mm, which is less than the voxel dimension. The mean GTV centroid position difference between ground truth and model estimation was less than 1 mm in all 3 orthogonal directions. Volumetric MRI from orthogonal cine acquisition with sparse priors is feasible by modeling prior knowledge through implicit neural representation learning. The model-reconstructed images showed sufficient accuracy in supporting 3D motion tracking of abdominal targets. By eliminating the need for large scale training datasets, the method promises to enable clinical implementation of 3D motion tracking for precision radiation therapy.

Intratumoral Dose Escalation Using Lattice Radiotherapy for Hepatocellular Carcinoma with Unfavorable Size and Location

Stereotactic body radiation therapy (SBRT) is a standard of care for unresectable hepatocellular carcinoma (HCC). However, its safe delivery is limited by tumor size and adjacent organs-at-risk (OARs). RTOG 1112 showed a survival benefit with local control in advanced HCC, but median dose was limited to 35 Gy in 5 fractions due to OARs. Here, we demonstrate the dosimetric feasibility of lattice radiation therapy (LRT) for dose escalation in advanced HCC. Five-fraction volumetric arc-based (VMAT) LRT plans were generated using a customized Python v3.6 script. For each combination of peak/valley doses and sphere size and spacing, a bounding box was generated around the gross tumor volume (GTV) and divided into equal segments in the x, y, and z planes. Individual spheres were constructed for a given parameter set and those fully encompassed within the target contracted by 2 cm were used to create peak dose targets with values of 30, 40, or 50 Gy. Valley dose target volumes over a range of 2 to 45 Gy were generated by subtracting an 8 mm expansion of the peak dose spheres from the overall target volume. Multi-criteria optimization (MCO) was applied to generate a final plan. The planning target volume (PTV) was a 5-mm uniform expansion from the GTV. All plans were generated at maximum inspiration on 4D-CT. OAR parameters were compared against a standard 5-fraction SBRT plan using Wilcoxon signed-rank testing. GTV and PTV measured 593 (23%) and 804 (32%) cm3, respectively, of a total liver volume of 2525 cm3. The minimum distance of GTV from stomach and duodenum was 6 mm and 2 mm, respectively. Plans were evaluated as per RTOG 1112 with stepwise reduction from a maximum PTV dose of 50 Gy based upon ability to meet mean liver dose (MLD, defined as liver-GTV) constraints; the 30 Gy threshold was the highest achievable. Of 7 eligible LRT plans, 5 with ablative 50 Gy peak doses were analyzed. Associated valley doses were 15 or 20 Gy. Median values of mean GTV and PTV doses for these plans were 36.2 (IQR, 34.6 - 37.8) and 32.9 (IQR, 31.3 - 33.4) Gy, respectively. A median of 12.4% (IQR, 7.4 - 28.4) of the GTV received a dose of 50 Gy. Median doses to 0.5 cc of stomach and duodenum were 16.7 Gy (range, 15.6 - 19.6) and 14.4 Gy (range, 12.3 - 23.9), respectively. The median value for MLD was 13.9 Gy (range, 13.6 to 14.8) and the median volume of normal liver spared 15 Gy was 1114 cm3 (range, 969 to 1154). These hepatic parameters were significantly decreased compared to a standard 30 Gy SBRT plan (18.1 Gy and 611.3 cc spared, p = 0.043 for both) which did not meet constraints. Dose escalation of advanced HCC using LRT is dosimetrically feasible. Though mean target doses remained limited by MLD, LRT allowed delivery of ablative dose to 12.4% of the GTV while meeting critical OAR constraints. Intratumoral dose-escalation may improve local control in advanced HCC patients.

Dose Assessment in Radiotherapy of Head and Neck Cancer after Metal Artifact Reduction in Neusoft-Philips Corporation CT Scanner: A Clinical Study

Purpose: Metal artifacts cause to increase in the uncorrected dose evaluation during radiotherapy planning. This study aimed to evaluate the probable difference of the dose parameters calculated by the Treatment Planning System (TPS) in radiotherapy of head and neck cancer before and after metal artifact correction in Neusoft-Philips Corporation Computed Tomography (CT) images.&#x0D; Materials and Methods: In the present study, the radiotherapy planning of the head and neck cancer from thirty patients was first performed on the CT default images with dental implants. The same processes were applied after performing a body standard metal kernel on the CT images to reduce the metal artifacts. The Gross Tumor Volume (GTV) and Organ At Risks (OARs) were contoured on the CT slices. The dosimetric parameters (mean, minimum, and maximum) for the GTV and OARs (eyes and spinal cord) were obtained for both sets of CT images (defaults and filtered). Wilcoxon signed-rank test was used to calculate the probability dose variations between the two sets.&#x0D; Results: There are significant differences in several dose parameters between the default and filtered CT images (P-value &lt; 0.05). These dosimetric parameters are related to the GTV (mean dose), spinal cord (minimum and mean doses), right eye (maximum dose), as well as left eye (mean dose). The average range of dose differences between the default and filtered images was obtained; 1.12%-3.11% for the GTV as well as 0.22%-12.05% for the OARs.&#x0D; Conclusion: Based on the results, the body standard metal kernel can cause a significant difference in several dosimetric parameters of GTV and OARs during the radiotherapy of head and neck cancer. Therefore, it is recommended to make a metal artifact correction on CT images for accurate dose calculation before designing a treatment plan.

Long-Term Outcomes of Endoscopic Resection versus Open Surgery for Locally Advanced Sinonasal Malignancies in Combination with Radiotherapy.

Objective Our objective was to compare the long-term outcomes of endoscopic resection versus open surgery in combination with radiotherapy for locally advanced sinonasal malignancies (SNMs). Methods Data for continuous patients with sinonasal squamous cell carcinoma and adenocarcinoma who received surgery (endoscopic or open surgery) combined with radiotherapy in our center between January 1999 and December 2016 were retrospectively reviewed. A 1:1 matching with propensity scores was performed. Overall survival (OS), progression-free survival (PFS), and local recurrence rate (LRR) were evaluated. Results We identified 267 eligible patients, 90 of whom were included after matching: 45 patients in the endoscopy group and 45 in the open group. The median follow-up time was 87 months. In the endoscopic group, 84.4% of patients received intensity-modulated radiotherapy (IMRT), with a mean gross tumor volume (GTV) dose of 68.28 Gy; in the open surgery group, 64.4% of patients received IMRT, with a mean GTV dose of 64 Gy. The 5-year OS, PFS, and LRR were 69.9, 58.6, and 24.5% in the endoscopic group and 64.6, 54.4, and 31.8% in the open surgery group, respectively. Multivariable regression analysis revealed that the surgical approach was not associated with lower OS, PFS, or LRR. The overall postoperative complications were 13% in the endoscopic group, while 21.7% in the open group. Conclusion For patients with locally advanced SNMs, minimally invasive endoscopic resection, in combination with a higher radiation dose and new radiation techniques such as IMRT, yields survival outcomes similar to those of open surgery in combination with radiotherapy.

A novel approach for dose painting radiotherapy of brain metastases guided by mr perfusion images.

To investigate the feasibility and dosimetric index features of dose painting guided by perfusion heterogeneity for brain metastasis (BMs) patients. A total of 50 patients with single BMs were selected for this study. CT and MR simulation images were obtained, including contrast-enhanced T1-weighted images (T1WI+C) and cerebral blood flow (CBF) maps from 3D-arterial spin labeling (ASL). The gross tumor volume (GTV) was determined by fusion of CT and T1WI+C images. Hypoperfused subvolumes (GTVH) with less than 25% of the maximum CBF value were defined as the dose escalation region. The planning target volume (PTV) and PTVH were calculated from GTV and GTVH respectively. The PTVN was obtained by subtracting PTVH from PTV, and conventional dose was given. Three kinds of radiotherapy plans were designed based on the CBF values. Plan 1 was defined as the conventional plan with an arbitrary prescription dose of 60 Gy for PTV. For dose painting, Plan 2 and Plan 3 escalated the prescription dose for PTVH to 72 Gy based on Plan 1, but Plan 3 removed the maximum dose constraint. Dosimetric indices were compared among the three plans. The mean GTV volume was 34.5 (8.4-118.0) cm3, and mean GTVH volume was 17.0 (4.5-58.3) cm3, accounting for 49.3% of GTV. Both conventional plan and dose painting plans achieved 98% target coverage. The conformity index of PTVH were 0.44 (Plan1), 0.64 and 0.72 (Plan 2 and Plan 3, P<0.05). Compared to Plan 1, the D2%, D98% and Dmean values of the PTVH escalated by 20.50%, 19.32%, and 19.60% in Plan 2 and by 24.88%, 17.22% and 19.22% in Plan 3 respectively (P<0.05). In the three plans, the index of achievement value for PTVH was between 1.01 and 1.03 (P<0.05). The dose increment rates of Plan 2 and Plan 3 for each organs at risk (OARs) was controlled at 2.19% - 5.61% compared with Plan 1. The doses received by OARs did not significantly differ among the three plans (P >0.05). BMs are associated with significant heterogeneity, and effective escalation of the dose delivered to target subvolumes can be achieved with dose painting guided by 3D-ASL without extra doses to OARs.

Can Post-Treatment Dosimetry Predict Clinical Outcomes in Segmental Transarterial Radioembolization of Hepatocellular Carcinoma?

<h3>Purpose/Objective(s)</h3> Prognosis for patients with hepatocellular carcinoma (HCC) is poor but segmental transarterial radioembolization (STARE) using Yttrium-90 (Y90) can achieve high rates of objective response (OR) in early-stage disease. Advances in 3D computational treatment planning systems (TPS) and nuclear imaging platforms allow for accurate calculation of Y90 activity distribution after STARE. However, post-STARE dosimetry is not used to guide current clinical practice. In this single center, retrospective study of Y90 STARE, we hypothesized that 3D post-treatment dosimetry derived from bremsstrahlung single photon emission computed tomography (SPECT/CT) correlates with meaningful clinical outcomes. <h3>Materials/Methods</h3> We reviewed 24 consecutive STARE of 23 HCC patients treated with glass microspheres from 2019 to 2021. Baseline characteristics and outcomes were collected by chart and imaging review. Commercial software was used to contour gross tumor volume (GTV) and liver on post-Y90 SPECT/CT aided by deformable fusion with prior diagnostic scans. Dose distribution was assessed using the Local Deposition Model based on SPECT/CT activity maps. Mean, minimum, and maximum GTV dose, volume of GTV receiving <100 Gy, < 70 Gy and < 50 Gy, minimum isodose encompassing the hottest 2% of the GTV (D2), D5, D30, D50, D70, D95, D98, and doses to nontumorous liver were captured. Kaplan-Meier (KM) survival, multivariate regression, and areas under the receiver operating characteristic curve (AUC) were estimated using STATA. <h3>Results</h3> Most patients were Child-Pugh A (19/23) and Barcelona Clinic Liver Cancer Stage B (14/23) at baseline. Median follow up time was 12 mo (range 1-24), median prescription 185 Gy (range 120-450), and median time to best mRECIST response was 5 mo (range 1 to 12). 92% of treatments (22/24) achieved OR and 62.5% (15/24) achieved complete response (CR). Solitary lesions with long axis < 4 cm were most likely to achieve CR. CR correlated with PFS (p=0.05, median PFS for non-CR 4 months, for CR not reached) and trended to significance in OS (p=0.10, median OS for non-CR 10 mo, for CR not reached). Mean GTV dose correlated with CR only on univariate analysis while GTV volume receiving <100 Gy was highly predictive of CR (AUC 0.92) with inflection point at 3 cc. Grade 2 and 3 toxicity rates were 16.6% and 8.3% with baseline bilirubin and albumin predictive of G2+ (AUC 0.84). <h3>Conclusion</h3> In this cohort of patients with HCC treated with STARE Y90, CR correlated with meaningful clinical outcomes (PFS and OS) and a high OR rate. Our findings suggest that (1) less than CR can be identified immediately using same-day post-treatment dosimetry with suboptimal target coverage at threshold volumes most predictive and (2) concordance between suboptimal dosimetry and early post-treatment diagnostic imaging can guide recommendations for additional liver-directed therapy, with intent to convert patients to CR and improve PFS and OS. This paradigm will be tested prospectively at our institution.

Patient-Specific Quality Assurance of Deformable Image Registrations Using Atlas for Adaptive Radiotherapy of Lung Cancer

<h3>Purpose/Objective(s)</h3> Evaluating the uncertainty of deformable image registration (DIR) is challenging because the ground truth is often unavailable. We developed an automated method to create realistic deformations via an atlas and assess DIR algorithms on a patient-specific level for adaptive radiotherapy. <h3>Materials/Methods</h3> A library of deformations was created by extracting the longitudinal anatomical changes observed from an atlas of 60 locally advanced non-small cell lung cancer patients treated with IMRT (60Gy, 30 fx). The deformation vector field (DVF) between the planning CT (pCT) and last weekly CBCT of an atlas patient was derived via a free-form DIR algorithm and served as a ground truth pattern. An inquiry patient was first matched to an atlas patient on gross tumor volume (GTV) location and volume. The pCT of an inquiry patient was then deformably registered to that of an atlas patient to establish a voxel-based correspondence. Then, the deformation pattern of the atlas patient was transferred to the inquiry patient pCT by applying the known DVF to the corresponding voxels, resulting in a digital CT phantom. Subsequently, this CT phantom was appended with CBCT artifacts using a physics-based augmentation (Alam, PMB 2021) to imitate a weekly CBCT. To evaluate DIRs, a large deformation diffeomorphic metric mapping (LDDMM) algorithm, and two commercial systems (C1 C2) were used between the phantom (both simulated CT and CBCT) and actual pCT of the inquiry patient. Derived DVFs were compared to the ground truth. The voxel-level geometric and dosimetric uncertainties of DIRs were calculated using the DVF95% errors, fraction of volume with ≤1.5mm errors (V1.5mm) and mean dose errors (D_mean) for GTV and esophagus. <h3>Results</h3> In a retrospective evaluation of 10 paired inquiry and atlas patients, the actual deformations observed between the pCT and weekly CBCTs of inquiry patients were well-contained by the combined patterns from the matched atlas, validating the feasibility of an atlas. LDDMM performed consistently well, especially for the CT-CBCT registration (p<0.01, two-tailed t-test). GTV mean dose is less sensitive to DIR errors than esophagus mean dose. <h3>Conclusion</h3> It is feasible to augment anatomical changes for a particular inquiry patient using deformation patterns from matched patients in an atlas and evaluate the uncertainty of DIR algorithms in realistic simulations. Integration of such an automated program facilitates the clinical implementation of adaptive radiotherapy that involves longitudinal imaging studies.

Association of Remnant Liver Dosage with Intra-Hepatic Recurrence and Distant Metastasis after Liver SBRT in Patients with HCC

<h3>Purpose/Objective(s)</h3> This study aims to evaluate whether dosimetric parameters affect the intrahepatic out-field recurrence or distant metastasis-free survival following the stereotactic body radiation therapy (SBRT) in patients with hepatocellular carcinoma (HCC). <h3>Materials/Methods</h3> A total of 76 patients with HCC who were treated with SBRT during 2015-2020 were included in this retrospective study. The clinical factors considered were intrahepatic out-field free survival (OutFFS), distant metastasis free survival (DMFS). The parameters of target and liver were documented including tumor diameters (TD), gross tumor volume (GTV), Liver minus GTV volume (LGV), Liver minus GTV mean dose (LGD). Multivariable Cox regression with forward stepwise selection was performed to identify independent risk factors for OutFFS and DMFS.Maximally selected rank statistics were used to determine the most informative cut-off value for age and LGD. <h3>Results</h3> The median follow-up was 28.2 months (range, 7.7-74.5 months). LGD higher than 12.54 Gy [HR, 0.861(0.747-0.993); <i>p</i> = 0.040] and age greater than 67-year-old [HR, 0.966(0.937-0.997); <i>p</i> = 0.030] are two independent predictors of OutFFS. Previous TACE treatment 0.117(0.015-0.891); <i>p</i> = 0.038] was an independent predictor of DMFS. <h3>Conclusion</h3> The results of this study suggest that the higher the dose received by the normal liver (greater than 12.54 Gy) the better the intrahepatic out field recurrence-free survival rate (OutFFS). Further study is warranted to confirm and to better understand this phenomenon.

Effect of the normal liver mean dose on intrahepatic recurrence in patients with hepatocellular carcinoma after receiving liver stereotactic body radiation therapy

Background and purposeThis study aims to evaluate whether dosimetric parameters affect the intrahepatic out-field recurrence or distant metastasis-free survival following the stereotactic body radiation therapy (SBRT) in patients with hepatocellular carcinoma (HCC). Materials and methodsA total of 76 patients with HCC who were treated with SBRT from January 2015 to May 2020 were included in this retrospective study. The main clinical endpoints considered were intrahepatic out-field free survival (OutFFS) and distant metastasis-free survival (DMFS). The target parameters and the liver were documented including tumor diameters, gross tumor volume (GTV), Liver minus GTV volume (LGV), and Liver minus GTV mean dose (LGD). Multivariable Cox regression with forward stepwise selection was performed to identify independent risk factors for OutFFS and DMFS. Maximally selected rank statistics were used to determine the most informative cut-off value for age and LGD. ResultsThe median follow-up was 28.2 months (range, 7.7–74.5 months). LGD higher than 12.54 Gy [HR, 0.861(0.747–0.993); p = 0.040] and age greater than 67-year-old [HR, 0.966(0.937–0.997); p = 0.030] are two independent predictors of OutFFS, previous TACE treatment [HR, 0.117(0.015–0.891); p = 0.038] was an independent predictor of DMFS. ConclusionsThe results of this study suggested that the higher the dose received by the normal liver (greater than 12.54 Gy) the better the intrahepatic out-field recurrence-free survival (RFS) rate. Further study is warranted to confirm and to better understand this phenomenon.

Conebeam CT‐guided 3D MLC‐based spatially fractionated radiation therapy for bulky masses

For fast, safe, and effective management of large and bulky (≥8 cm) non‐resectable tumors, we have developed a conebeam CT‐guided three‐dimensional (3D)‐conformal MLC‐based spatially fractionated radiation therapy (SFRT) treatment. Using an in‐house MLC‐fitting algorithm, Millennium 120 leaves were fitted to the gross tumor volume (GTV) generating 1‐cm diameter holes at 2‐cm center‐to‐center distance at isocenter. SFRT plans of 15 Gy were generated using four to six coplanar crossfire gantry angles 60° apart with a 90° collimator, differentially weighted with 6‐ or 10‐MV beams. A dose was calculated using AcurosXB algorithm, generating sieve‐like dose channels without post‐processing the physician‐drawn GTV contour within an hour of CT simulation allowing for the same day treatment. In total, 50 extracranial patients have been planned and treated using this method, comprising multiple treatment sites. This novel MLC‐fitting algorithm provided excellent dose parameters with mean GTV (V7.5 Gy) and mean GTV doses of 53.2% and 7.9 Gy, respectively, for 15 Gy plans. Average peak‐to‐valley dose ratio was 3.2. Mean beam‐on time was 3.32 min, and treatment time, including patient setup and CBCT to beam‐off, was within 15 min. Average 3D couch correction from original skin‐markers was <1.0 cm. 3D MLC‐based SFRT plans enhanced target dose for bulky masses, including deep‐seated large tumors while protecting skin and adjacent critical organs. Additionally, it provides the same day, safe, effective, and convenient treatment by eliminating the risk to therapists and patients from heavy gantry‐mounted physical GRID‐block—we recommend other centers to use this simple and clinically useful method. This rapid SFRT planning technique is easily adoptable in any radiation oncology clinic by eliminating the need for plan optimization and patient‐specific quality assurance times while providing dosimetry information in the treatment planning system. This potentially allows for dose‐escalation to deep‐seated masses to debulk unresectable large tumors providing an option for neoadjuvant treatment. An outcome study of clinical trial is underway.

A Dosimetric Comparison of Lattice, Brass, and Proton Grid Therapy Treatment Plans

PurposeOur purpose was to dosimetrically compare volumetric modulated arc therapy (VMAT) lattice radiation therapy (LRT), brass, and proton grid therapy planning techniques and suggest potential clinical applications for each. Methods and MaterialsFour plans delivering 20 Gy in 1 fraction were created for each of 22 patients. Brass and proton grid plans used a single static field and the same beam angle. Proton grid plans used the same beam size and spacing as the brass block. Two VMAT LRT plans were generated for each patient: one with 1-cm diameter lattice points spaced 2-cm center-to-center (2-cm VMAT) and another with 1.5-cm diameter lattice points spaced 3-cm center-to-center (3- cm VMAT). Maximum, minimum, mean, and equivalent uniform dose and the dose to 90%, 50%, 20%, 10%, and 5% (D90%[%], D50%[%], etc) of gross tumor volume (GTV) were reported. D10%/D90% characterized dose heterogeneity. Normal tissue dose was generalized by the maximum dose and volume in cubic centimeters of tissue outside the GTV receiving 30% and 50% of prescription (body-GTV V30%[cm3]; body-GTV V50%[cm3]). ResultsVMAT LRT plans delivered the highest maximum GTV doses while brass and proton plans delivered higher D5%(%), D10%(%), and D20%(%) values. D50%(%), D90%(%), and minimum dose varied little between plan types. Proton and brass plans had the highest dose heterogeneity. Two-centimeter VMAT and brass grid plans had the highest mean GTV doses. Two-centimeter VMAT plans had the highest equivalent uniform dose, followed by 3-cm VMAT, brass, and proton plans. VMAT LRT plans exhibited the lowest normal tissue maximum and body GTV V30%(cm3) and body GTV V50%(cm3) values. ConclusionsAn in-depth comparison of target and normal tissue dosimetric parameters for common photon and proton grid therapy planning techniques was made. Strengths of each plan type were noted leading to general recommendations on usage.

Radial Data Mining to Identify Density-Dose Interactions That Predict Distant Failure Following SABR.

PurposeLower dose outside the planned treatment area in lung stereotactic radiotherapy has been linked to increased risk of distant metastasis (DM) possibly due to underdosage of microscopic disease (MDE). Independently, tumour density on pretreatment computed tomography (CT) has been linked to risk of MDE. No studies have investigated the interaction between imaging biomarkers and incidental dose. The interaction would showcase whether the impact of dose on outcome is dependent on imaging and, hence, if imaging could inform which patients require dose escalation outside the gross tumour volume (GTV). We propose an image-based data mining methodology to investigate density–dose interactions radially from the GTV to predict DM with no a priori assumption on location.MethodsDose and density were quantified in 1-mm annuli around the GTV for 199 patients with early-stage lung cancer treated with 60 Gy in 5 fractions. Each annulus was summarised by three density and three dose parameters. For parameter combinations, Cox regressions were performed including a dose–density interaction in independent annuli. Heatmaps were created that described improvement in DM prediction due to the interaction. Regions of significant improvement were identified and studied in overall outcome models.ResultsDose–density interactions were identified that significantly improved prediction for over 50% of bootstrap resamples. Dose and density parameters were not significant when the interaction was omitted. Tumour density variance and high peritumour density were associated with DM for patients with more cold spots (less than 30-Gy EQD2) and non-uniform dose about 3 cm outside of the GTV. Associations identified were independent of the mean GTV dose.ConclusionsPatients with high tumour variance and peritumour density have increased risk of DM if there is a low and non-uniform dose outside the GTV. The dose regions are independent of tumour dose, suggesting that incidental dose may play an important role in controlling occult disease. Understanding such interactions is key to identifying patients who will benefit from dose-escalation. The methodology presented allowed spatial dose–density interactions to be studied at the exploratory stage for the first time. This could accelerate the clinical implementation of imaging biomarkers by demonstrating the impact of incidental dose for tumours of varying characteristics in routine data.

Feasibility Study of 3D-VMAT-Based GRID Therapy.

Background: Spatially fractionated radiotherapy (GRID) could effectively de-bulk tumor volumes for shallow and deep-seated locally advanced tumors. A new treatment planning method using the three-dimensional-volumetric modulated arc therapy (VMAT) technique combined with a novel, software-generated, virtual GRID block (VGB) was developed which allows better conformity plans (VMAT-GRID) and maintain the GRID dosimetric characteristics. The dosimetric metrics calculated via the valley/peak ratio (Dmin/Dmax), D90/D10, gross tumor volume (GTV) mean dose (Dmean), GTV equivalent uniform dose (EUD), and normal tissue maximum dose. Methods: Twenty-five patients with tumor volumes ranging between 71.6 cc and 4683 cc at various tumor sites were retrospectively studied. The prescription was 20 Gy to the maximum point of GTV in a single fraction, and the VMAT-GRID plan was generated using 6 MV/10 MV flattening-filter-free beams. Results: The optimized VGB was designed with the median center-to-center distance of 27 mm, and 9 mm for the median diameter of the opening area in this study. These 2 values can be used to design any optimized VGB, the final VGB may be modified to generate a patient-specific VGB. The median GTV mean dose was 918 (877- 938) cGy, and the median GTV EUD dose was 818 (597-916) cGy. In terms of dose inhomogeneity, the median valley-to-peak dose ratio was 0.07 (0.02-0.26); and the median ratio of D90/D10 was 0.70 (0.38-0.94). For the organ-at-risk doses, there was a rapid dose drop-off in the normal tissue area immediately adjacent to the target, and the maximum global doses were all located inside the GTV. Conclusion: Our results indicated that the VMAT-GRID planning approach could successfully deliver dose with acceptable GRID dose metric while sparing the normal tissue especially in the region near the target due to the rapid dose drop-off and restricting maximum dose inside the target.