Radiotherapy For Lung Tumors Research Articles

Optimizing target and diaphragmatic configuration, and dosimetric benefits using continuous positive airway pressure in stereotactic ablative radiotherapy for lung tumors.

This study aimed to evaluate the impact of facilitating target delineation of continuous positive airway pressure (CPAP) in patients undergoing stereotactic ablative radiation therapy (SABR) for lung tumors by lung expansion and respiratory motion management. We performed a prospective single-institutional trial of patients who were diagnosed with either primary lung cancer or lung metastases and received SABR with a dose of 40 to 60 Gy in 4 fractions. Four-dimensional computed tomography simulations were conducted for each patient: once without CPAP and again with CPAP. Thirty-two patients with 39 tumors were analyzed, after the withdrawal of five patients due to discomfort. For 26 tumors separated from the diaphragm, CPAP significantly increased the superoinferior distance between the tumor and the diaphragm (5.96 cm vs. 8.06 cm; p < 0.001). For 13 tumors located adjacent to the diaphragm, CPAP decreased the overlap of planning target volume (PTV) with the diaphragm significantly (6.32 cm3 vs. 4.09 cm3; p = 0.002). PTV showed a significant reduction with CPAP (25.06 cm3 vs. 22.52 cm3, p = 0.017). In dosimetric analyses, CPAP expanded lung volume by 58.4% with a significant reduction in mean dose and V5 to V40. No more than grade 2 adverse events were reported. This trial demonstrated significant improvement of CPAP in target delineation uncertainties for lung SABR, with dosimetric benefits, a favorable safety profile and tolerability. Further investigation is warranted to explore the role of CPAP as a novel strategy for respiratory motion management.

MRI-based ventilation and perfusion imaging to predict radiation-induced pneumonitis in lung tumor patients at a 0.35 T MR-Linac

Background and purpose:Radiation-induced pneumonitis (RP), diagnosed 6–12 weeks after treatment, is a complication of lung tumor radiotherapy. So far, clinical and dosimetric parameters have not been reliable in predicting RP. We propose using non-contrast enhanced magnetic resonance imaging (MRI) based functional parameters acquired over the treatment course for patient stratification for improved follow-up. Materials and methods:23 lung tumor patients received MR-guided hypofractionated stereotactic body radiation therapy at a 0.35T MR-Linac. Ventilation- and perfusion-maps were generated from 2D-cine MRI-scans acquired after the first and last treatment fraction (Fx) using non-uniform Fourier decomposition. The relative differences in ventilation and perfusion between last and first Fx in three regions (planning target volume (PTV), lung volume receiving more than 20Gy (V20) excluding PTV, whole tumor-bearing lung excluding PTV) and three dosimetric parameters (mean lung dose, V20, mean dose to the gross tumor volume) were investigated. Univariate receiver operating characteristic curve - area under the curve (ROC–AUC) analysis was performed (endpoint RP grade≥1) using 5000 bootstrapping samples. Differences between RP and non-RP patients were tested for statistical significance with the non-parametric Mann–Whitney U test (α=0.05). Results:14/23 patients developed RP of grade≥1 within 3 months. The dosimetric parameters showed no significant differences between RP and non-RP patients. In contrast, the functional parameters, especially the relative ventilation difference in the PTV, achieved a p-value<0.05 and an AUC value of 0.84. Conclusion:MRI-based functional parameters extracted from 2D-cine MRI-scans were found to be predictive of RP development in lung tumor patients.

Secretory factors released from high dose radiation-activated osteoclasts increase the expression level of pain-associated neuropeptides in sensory neuronal cultures.

Stereotactic Body Radiation Therapy for lung tumors near the chest wall often causes significant chest wall pain (CWP), negatively impacting patients' quality of life. The mechanisms behind SBRT-induced CWP remain unclear and may involve multiple factors. We investigated the potential crosstalk between radiation-activated osteoclasts and sensory neurons, focusing on osteoclast-derived factors in CWP. Using the murine pre-osteoclast cell line Raw264.7, we induced differentiation with RANKL, followed by 10Gy gamma-irradiation. Conditioned media from these irradiated osteoclasts was used to treat sensory neuronal cultures from mouse dorsal root ganglia. Neuronal cultures were also directly exposed to 10Gy radiation, with and without osteoclast co-culture. Analysis of osteoclast markers and pain-associated neuropeptides was conducted using RT-qPCR and histochemical staining. Osteoclast differentiation and activity were inhibited using Osteoprotegerin and risedronate. Results showed that high-dose radiation significantly increased osteoclast size, resorption pit size, and activity biomarkers. Neurons treated with CM from irradiated osteoclasts showed increased expression of pain-associated neuropeptides CGRP and Substance P, which was mitigated by osteoprotegerin and risedronate. This study suggests that high-dose radiation enhances osteoclast activity, upregulating pain-associated neuropeptides in sensory neurons, and that inhibitors like osteoprotegerin and risedronate may offer therapeutic strategies for managing radiation-induced pain.

Impact of setup and geometric uncertainties on the robustness of free-breathing photon radiotherapy of small lung tumors

Purpose:Respiratory motion and patient setup error both contribute to the dosimetric uncertainty in radiotherapy of lung tumors. Managing these uncertainties for free-breathing treatments is usually done by margin-based approaches or robust optimization. However, breathing motion can be irregular and concerns have been raised for the robustness of the treatment plans. We have previously reported the dosimetric effects of the respiratory motion, without setup uncertainties, in lung tumor photon radiotherapy using free-breathing images. In this study, we include setup uncertainty. Methods:Tumor positions from cine-CT images acquired in free-breathing were combined with per-fraction patient shifts to simulate treatment scenarios. A total of 14 patients with 300 tumor positions were used to evaluate treatment plans based on 4DCT. Four planning methods aiming at delivering 54 Gy as median tumor dose in three fractions were compared. The planning methods were denoted robust 4D (RB4), isodose to the PTV with a central higher dose (ISD), the ISD method normalized to the intended median tumor dose (IRN) and homogeneous fluence to the PTV (FLU). Results:For all planning methods 95% of the intended dose was achieved with at least 90% probability with RB4 and FLU having equal CTV D50% values at this probability. FLU gave the most consistent results in terms of CTV D50% spread and dose homogeneity. Conclusions:Despite the simulated patient shifts and tumor motions being larger than observed in the 4DCTs the dosimetric impact was suggested to be small. RB4 or FLU are recommended for the planning of free-breathing treatments.

Robust optimization of the Gross Tumor Volume compared to conventional Planning Target Volume-based planning in photon Stereotactic Body Radiation Therapy of lung tumors.

Robust optimization has been suggested as an approach to reduce the irradiated volume in lung Stereotactic Body Radiation Therapy (SBRT). We performed a retrospective planning study to investigate the potential benefits over Planning Target Volume (PTV)-based planning. Thirty-nine patients had additional plans using robust optimization with 5-mm isocenter shifts of the Gross Tumor Volume (GTV) created in addition to the PTV-based plan used for treatment. The optimization included the mid-position phase and the extreme breathing phases of the 4D-CT planning scan. The plans were compared for tumor coverage, isodose volumes, and doses to Organs At Risk (OAR). Additionally, we evaluated both plans with respect to observed tumor motion using the peak tumor motion seen on the planning scan and cone-beam CTs. Statistically significant reductions in irradiated isodose volumes and doses to OAR were achieved with robust optimization, while preserving tumor dose. The reductions were largest for the low-dose volumes and reductions up to 188 ccm was observed. The robust evaluation based on observed peak tumor motion showed comparable target doses between the two planning methods. Accumulated mean GTV-dose was increased by a median of 4.46 Gy and a non-significant increase of 100 Monitor Units (MU) was seen in the robust optimized plans. The robust plans required more time to prepare, and while it might not be a feasible planning strategy for all lung SBRT patients, we suggest it might be useful for selected patients.

Impact of different respiratory gating methods on target delineation and a radiotherapy plan for solitary pulmonary tumors.

Respiratory movement has an important impact on the radiotherapy for lung tumor. Respiratory gating technology is helpful to improve the accuracy of target delineation. This study investigated the value of prospective and retrospective respiratory gating simulations in target delineation and radiotherapy plan design for solitary pulmonary tumors (SPTs) in radiotherapy. The enrolled patients underwent CT simulation with three-dimensional (3D) CT non gating, prospective respiratory gating, and retrospective respiratory gating simulation. The target volumes were delineated on three sets of CT images, and radiotherapy plans were prepared accordingly. Tumor displacements and movement information obtained using the two respiratory gating approaches, as well as the target volumes and dosimetry parameters in the radiotherapy plan were compared. No significant difference was observed in tumor displacement measured using the two gating methods (p > 0.05). However, the internal gross tumor volumes (IGTVs), internal target volumes (ITVs), and planning target volumes (PTVs) based on the retrospective respiratory gating simulation were larger than those obtained using prospective gating (group A: pIGTV = 0.041, pITV = 0.003, pPTV = 0.008; group B: pIGTV = 0.025, pITV = 0.039, pPTV = 0.004). The two-gating PTVs were both smaller than those delineated on 3D non gating images (p < 0.001). V5Gy, V10Gy, V20Gy, V30Gy, and mean lung dose in the two gated radiotherapy plans were lower than those in the 3D non gating plan (p < 0.001); however, no significant difference was observed between the two gating plans (p > 0.05). The application of respiratory gating could reduce the target volume and the radiation dose that the normal lung tissue received. Compared to prospective respiratory gating, the retrospective gating provides more information about tumor movement in PTV.

3226: Outcomes and Side Effects of Image-Guided Single-Dose Stereotactic Radiotherapy for Lung Tumors

3226: Outcomes and Side Effects of Image-Guided Single-Dose Stereotactic Radiotherapy for Lung Tumors

Inverse planning of lung radiotherapy with photon and proton beams using a discrete ordinates Boltzmann solver

Objective. A discrete ordinates Boltzmann solver has recently been developed for use as a fast and accurate dose engine for calculation of photon and proton beams. The purpose of this study is to apply the algorithm to the inverse planning process for photons and protons and to evaluate the impact that this has on the quality of the final solution. Approach. The method was implemented into an iterative least-squares inverse planning optimiser, with the Boltzmann solver used every 20 iterations over the total of 100 iterations. Elemental dose distributions for the intensity modulation and the dose changes at the intermediate iterations were calculated by a convolution algorithm for photons and a simple analytical model for protons. The method was evaluated for 12 patients in the heterogeneous tissue environment encountered in radiotherapy of lung tumours. Photon arc and proton arc treatments were considered in this study. The results were compared with those for use of the Boltzmann solver solely at the end of inverse planning or not at all. Main results. Application of the Boltzmann solver at the end of inverse planning shows the dose heterogeneity in the planning target volume to be greater than calculated by convolution and empirical methods, with the median root-mean-square dose deviation increasing from 3.7 to 5.3 for photons and from 1.9 to 3.4 for proton arcs. Use of discrete ordinates throughout inverse planning enables homogeneity of target coverage to be maintained throughout, the median root-mean-square dose deviation being 3.6 for photons and 2.3 for protons. Dose to critical structures is similar with discrete ordinates and conventional methods. Time for inverse planning with discrete ordinates takes around 1–2 h using a contemporary computing environment. Significance. By incorporating the Boltzmann solver into an iterative least squares inverse planning optimiser, accurate dose calculation in a heterogeneous medium is obtained throughout inverse planning, with the result that the final dose distribution is of the highest quality.

Predicting Local Control with Dosimetric Parameters in Patients Receiving Individualized Stereotactic Ablative Radiotherapy for Lung Tumors

Stereotactic ablative radiotherapy (SABR) is an effective treatment option for lung tumors. The individualized lung tumor SABR (iSABR) trial was a phase II single-arm study that personalized lung tumor SABR dose and fractionation based on tumor size, location, and histology with very low rates of local recurrence (LR). A secondary analysis of this trial was conducted to assess for potential dosimetric predictors of LR, in order to help guide future clinical treatment planning. From 2011 to 2018, local, regional and distant recurrence data were prospectively collected from 204 patients (261 lung SABR treatments) enrolled in a prospective trial. Baseline characteristics and treatment details were evaluated. Dosimetric and treatment plan parameters were evaluated for their potential to predict LR, using logistic regression and chi-squared analyses. The majority of treated tumors were peripheral (71%, vs 29% central), primary lesions (76%, versus 24% metastatic), and of adenocarcinoma histology (67%, versus 13% squamous cell carcinoma and 19% other). The median follow-up was 24 months (range 2-95). Twenty-seven (10.3%) LRs occurred, with a median time to LR of 15 months (range 6-81 months). There were no significant associations between the overall cohort and the dosimetric parameters. However, for the multi-fraction cohort, an increased proportion of the PTV receiving 110% and 115% of the prescription dose were associated with lower LR (p = 0.01 and p = 0.01 respectively). Specifically for the 50 Gy in 4 fraction cohort, an increased D1cc, D0.03cc, as well as the proportion of the PTV receiving 110%, 115%, and 120% of the prescription dose were associated with lower LR (p < 0.001, p = 0.001, p = 0.003, p < 0.001, p = 0.004, respectively). There was no association of LR with prescription dose expressed as biologically effective dose using an alpha/beta of 10 Gy (BED10), D99%, or single- versus multi-fraction regimens. SABR for lung tumors using the individualized protocol on this trial showed excellent LR rates. We identified dosimetric parameters that were associated with LR, including V110% and V115% within the multi-fraction cohort, as well as the 50 Gy in 4 fraction cohort the D1cc, D0.03cc, and proportions of the PTV receiving 110%, 115%, and 120% of the prescription dose in the 50 Gy in 4 fraction cohort. Optimal thresholds for these parameters will be identified in further analyses. There did not appear to be an association with LR and BED10, D99%, or comparing single- vs multi-fraction regimens.

Individualized Stereotactic Ablative Radiotherapy for Lung Tumors

Stereotactic ablative radiotherapy (SABR) is used for treating lung tumors but can cause toxic effects, including life-threatening damage to central structures. Retrospective data suggested that small tumors up to 10 cm3 in volume can be well controlled with a biologically effective dose less than 100 Gy. To assess whether individualizing lung SABR dose and fractionation by tumor size, location, and histological characteristics may be associated with local tumor control. This nonrandomized controlled trial (the iSABR trial, so named for individualized SABR) was a phase 2 multicenter trial enrolling participants from November 15, 2011, to December 5, 2018, at academic medical centers in the US and Japan. Data were analyzed from December 9, 2020, to May 10, 2023. Patients were enrolled in 3 groups according to cancer type: initial diagnosis of non-small cell lung cancer (NSCLC) with an American Joint Committee on Cancer 7th edition T1-3N0M0 tumor (group 1), a T1-3N0M0 new primary NSCLC with a history of prior NSCLC or multiple NSCLCs (group 2), or lung metastases from NSCLC or another solid tumor (group 3). Up to 4 tumors were treated with once-daily SABR. The dose ranged from 25 Gy in 1 fraction for peripheral tumors with a volume of 0 to 10 cm3 to 60 Gy in 8 fractions for central tumors with a volume greater than 30 cm3. Per-group freedom from local recurrence (same-lobe recurrence) at 1 year, with censoring at time of distant recurrence, death, or loss to follow-up. In total, 217 unique patients (median [IQR] age, 72 [64-80] years; 129 [59%] male; 150 [69%] current or former smokers) were enrolled (some multiple times). There were 240 treatment courses: 79 in group 1, 82 in group 2, and 79 in group 3. A total of 285 tumors (211 [74%] peripheral and 74 [26%] central) were treated. The most common dose was 25 Gy in 1 fraction (158 tumors). The median (range) follow-up period was 33 (2-109) months, and the median overall survival was 59 (95% CI, 49-82) months. Freedom from local recurrence at 1 year was 97% (90% CI, 91%-99%) for group 1, 94% (90% CI, 87%-97%) for group 2, and 96% (90% CI, 89%-98%) for group 3. Freedom from local recurrence at 5 years ranged from 83% to 93% in the 3 groups. The proportion of patients with grade 3 to 5 toxic effects was low, at 5% (including a single patient [1%] with grade 5 toxic effects). The results of this nonrandomized controlled trial suggest that individualized SABR (iSABR) used to treat lung tumors may allow minimization of treatment dose and is associated with excellent local control. Individualized dosing should be considered for use in future trials. ClinicalTrials.gov Identifier: NCT01463423.

Fixation rate of fiducial gold markers in each segmental bronchus for stereotactic body radiotherapy

BackgroundIn real-time tumor-tracking radiotherapy for lung tumors, placement of fiducials, such as a gold marker (GM), is necessary. However, transbronchially placed GMs often drop out spontaneously. Therefore, we aimed to clarify the fixation rate of GMs in each segmental bronchus. MethodsIn this study, we examined the fixation rates of 791 GMs placed in 235 patients (259 procedures), from November 2011 to November 2020, at a single facility. The relationship between the elapsed time and the fixation rate was assessed using the Kaplan–Meier method. Moreover, we measured the distance between the GM and the chest wall (DMC), as confirmed using planning computed tomography, and analyzed the relationship of this distance with the fixation rate. ResultsOverall, 28.8% of GMs dropped out within 10 days of placement. The fixation rate of GMs in the bronchi was significantly lower in the upper lobe than in the other lobes, in both lungs (right, p < 0.01; left, p = 0.05). Moreover, in the left upper lobe, the fixation rate of GMs was significantly lower in B1+2 than in B3 (p = 0.0181). In addition, the group with a short DMC had a significantly higher GM fixation rate. (p < 0.01). ConclusionsThe fixation rate of GMs was lower in the upper lobes than in the lower lobes. Additionally, the fixation rate was lower in B1+2 than in B3. Shorter DMCs were associated with higher GM fixation rates.

Adaptive hypofractionted and stereotactic body radiotherapy for lung tumors with real-time MRI guidance.

The treatment of central and ultracentral lung tumors with radiotherapy remains an ongoing clinical challenge. The risk of Grade 5 toxicity with ablative radiotherapy doses to these high-risk regions is significant as shown in recent prospective studies. Magnetic resonance (MR) image-guided adaptive radiotherapy (MRgART) is a new technology and may allow the delivery of ablative radiotherapy to these high-risk regions safely. MRgART is able to achieve this by utilizing small treatment margins, real-time gating/tracking and on-table plan adaptation to maintain dose to the tumor but limit dose to critical structures. The process of MRgART is complex and has nuances and challenges for the treatment of lung tumors. We outline the critical steps needed for appropriate delivery of MRgART for lung tumors safely and effectively.

Dose Prescription to Isodose Lines in Static Multi-Beam Stereotactic Body Radiotherapy for Lung Tumors: Which Line Is Optimal?

This study investigated the appropriate dose prescription method in static multi-beam stereotactic body radiotherapy for lung tumors. Static multi-beam stereotactic body radiotherapy is a mainstream treatment in Japan. Based on the hypothesis that dose prescription to lower isodose lines may improve planning target volume dose coverage and decrease doses to organs at risk, we investigated changes in dose-volume histograms with prescription to various isodose lines for planning target volume in static multi-beam stereotactic body radiotherapy. In all treatment plans, 45 Gy in 4 fractions were prescribed to 95% of the planning target volume. By adjusting the leaf margins of each beam, various prescription isodose lines encompassing 95% volume of the planning target volume were generated. The prescription isodose lines investigated were 40, 50, 60, 70, 80 and 90% lines relative to the maximum dose of each planning target volume. The conformity index, homogeneity index, mean lung dose, and V5-V40 of the lung were evaluated. The dose was calculated by the adaptive convolve algorithm. The conformity index was lowest in the 70% or 80% isodose plan. The mean lung doses and V10-V40 of the lung decreased steeply from the 90% to the 70% isodose plan, and was lowest in the 60% and 70% isodose plans. These indices increased in the 40% and 50% isodose plans. The optimal stereotactic body radiotherapy plans appeared to be dose prescription to the 60% or 70% isodose line. Further investigation is warranted to clarify the advantage of using this method clinically.

Local Recurrence Risk Score to Predict Relapse after Stereotactic Body Radiation Therapy for Lung Tumors.

After stereotactic body radiation therapy (SBRT) for lung tumors, follow-up CT scans remain a pitfall. The early detection of local relapse is essential to propose a new treatment. We aim to create a local recurrence predictive score using pre- and post-therapeutic imaging criteria and test it on a validation cohort. Between February 2011 and July 2016, lung tumors treated by SBRT with available pretreatment fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) and follow-up CT scans were retrospectively analyzed. The risk factors associated with relapse were identified by univariate logistic regression on a train cohort. The score was created using these factors, merging clinical and imaging criteria associated with local relapse, and then tested on an independent validation cohort. Overall and local relapse-free survival at 1 and 3 years were recorded. Twenty-eight patients were included in the train cohort and ten in the derivation cohort (male 74%, median age 70 ± 12 years). Five variables significantly associated with local recurrence (female gender; sequential enlargement; craniocaudal growing; bulging margins; standardized uptake value (SUVmax &gt; 5.5)) were combined to create the score on five points. With the threshold &gt;2.5/5, the sensitivity and specificity of the score on the validation cohort were 100% and 88%, respectively. Overall survival and local relapse-free survival at 1 and 3 years were 89% and 42%, and 89% and 63%, respectively. The local recurrence risk score created has high sensitivity (100%) and specificity (88%), upon independent validation cohort, to detect local relapse. This score is easy to use in daily clinical practice.

Dosimetric robustness of lung tumor photon radiotherapy evaluated from multiple event CT imaging

Purpose:Intrafractional respiratory motion is a concern for lung tumor radiotherapy but full evaluation of its impact is hampered by the lack of images representing the true motion. This study presents a novel evaluation using free-breathing images acquired over realistic treatment times to study the dosimetric impact of respiratory motion in photon radiotherapy. Methods:Cine-CT images of 14 patients with lung cancer acquired during eight minutes of free-breathing at three occasions were used to simulate dose tracking of four different planning methods. These methods aimed to deliver 54 Gy in three fractions to D50% of the target and were denoted as robust 4D (RB4), homogeneous fluence to the ITV (FLU) and an isodose prescription to the ITV with a high central dose (ISD), concurrently renormalized (IRN). Differences in dose coverage probability and homogeneity between the methods were quantified. Correlations between underdosage and attributes regarding the tumor and its motion were investigated. Results:Despite tumor motion amplitudes being larger than in the 4DCT all but FLU achieved the intended CTV D50% for the cohort average. For all methods but IRN at least 93% of the patients would have received 95% of the intended dose. No differences in D50% were found between RB4 and ISD nor IRN. However, RB4 led to better homogeneity. Conclusions:Tumor motion in free-breathing not covered by the 4DCT had a small impact on dose. The RB4 is recommended for planning of free-breathing treatments. No factor was found that consistently correlated dose degradation with patient or motion attributes.

OA14.04 Chest Wall Toxicity after Individualized Stereotactic Ablative Radiotherapy for Lung Tumors

Chest wall toxicity (CWT), comprising chest wall (CW) pain and radiation-induced rib fracture, is a common adverse effect of lung stereotactic ablative radiotherapy (SABR) for treatments near the CW. However, there is currently no clear consensus on dosimetric constraints or fractionation schemes (single versus multiple) to mitigate this toxicity. The goal of this analysis is to identify predictive dosimetric parameters for CWT and to compare outcomes for patients undergoing single- vs. multi-fraction SABR.

A new method for assessing lung tumor motion in radiotherapy using dynamic chest radiography.

Dynamic chest radiography (DCR) is a recent advanced modality to acquire dynamic and functional images. We developed a new method using DCR and the free analysis software, Kinovea, to assess lung tumor motion. This study aimed to demonstrate the usefulness of our method. Phantom and clinical studies were performed. In the phantom study, dynamic images of a moving lead sphere were acquired using DCR, and the motion of the phantom was tracked using Kinovea in a DCR video. The amplitude of phantom motion was measured and compared with a predetermined baseline amplitude. In a clinical study, DCR and respiratory‐gated four‐dimensional computed tomography (4D‐CT) were performed on 15 patients who underwent stereotactic body radiation therapy for lung tumors. The amplitudes of tumor motion in DCR and 4D‐CT were measured in the superior‐inferior (SI), left‐right (LR), and anterior‐posterior (AP) directions, and the square root of the sum of squares (SRSS) of the amplitude was calculated in all directions. Spearman's rank correlation and the Wilcoxon signed‐rank test were performed to determine the correlations of the amplitudes of tumor motion obtained using DCR and 4D‐CT. In the phantom study, the absolute mean error between the measured and predetermined amplitudes was 0.60 mm (range: 0.061.53 mm). In the clinical study, the amplitudes of tumor motion obtained using DCR correlated significantly with those of 4D‐CT in the SI and LR directions, as did the SRSS values. The median amplitudes for DCR were significantly higher than those for 4D‐CT in all (SI, LR, and AP) directions, as were the SRSS values. Our proposed method based on DCR and Kinovea is useful for assessing lung tumor motion, visually and quantitatively. Therefore, DCR has potential as a new modality for evaluating lung tumor motion in radiotherapy.

Dosimetric effects of respiratory motion during stereotactic body radiation therapy of lung tumors

Background Respiratory-induced lung tumor motion may affect the delivered dose in stereotactic body radiation therapy (SBRT). Previous studies are often based on phantom studies for one specific treatment technique. In this study, the dosimetric effect of tumor motion was quantified in real patient geometries for different modulated treatments and tumor motion amplitudes for lung-SBRT. Material and Methods A simulation method using deformable image registrations and 4-dimensional computed tomographies (4DCT) was developed to assess the dosimetric effects of tumor motion. The method was evaluated with ionization chamber and Gafchromic film measurements in a thorax phantom and used to simulate the effect for 15 patients with lung tumors moving 7.3–27.4 mm. Four treatment plans with different complexities were created for each patient and the motion-induced dosimetric effect to the gross tumor volume (GTV) was simulated. The difference between the planned dose to the static tumor and the simulated delivered dose to the moving tumor was quantified for the near minimum (D98%), near maximum (D2%) and mean dose (Dmean) to the GTV as well as the largest observed local difference within the GTV (Maxdiff). Results No correlation was found between the dose differences and the tumor motion amplitude or plan complexity. However, the largest deviations were observed for tumors moving >15.0 mm. The simulated delivered dose was within 2.5% from the planned dose for D98% (tumors moving <15 mm) and within 3.3% (tumors moving >15 mm). The corresponding values were 1.7% vs. 6.4% (D2%); 1.7% vs. 2.4% (Dmean) and 8.9% vs. 35.2% (Maxdiff). Using less complex treatment techniques minimized Maxdiff for tumors moving >15.0 mm. Conclusion The dosimetric effects of respiratory-induced motion during lung SBRT are patient and plan specific. The magnitude of the dosimetric effect cannot be assessed solely based upon tumor motion amplitude or plan complexity.

Improved Tumor Image Estimation in X-Ray Fluoroscopic Images by Augmenting 4DCT Data for Radiotherapy

Measurement of tumor position is important for the radiotherapy of lung tumors with respiratory motion. Although tumors can be observed using X-ray fluoroscopy during radiotherapy, it is often difficult to measure tumor position from X-ray image sequences accurately because of overlapping organs. To measure tumor position accurately, a method for extracting tumor intensities from X-ray image sequences using a hidden Markov model (HMM) has been proposed. However, the performance of tumor intensity extraction depends on limited knowledge regarding the tumor motion observed in the four-dimensional computed tomography (4DCT) data used to construct the HMM. In this study, we attempted to improve the performance of tumor intensity extraction by augmenting 4DCT data. The proposed method was tested using simulated datasets of X-ray image sequences. The experimental results indicated that the HMM using the augmentation method could improve tumor-tracking performance when the range of tumor movement during treatment differed from that in the 4DCT data.

Magnetic resonance guided adaptive stereotactic body radiotherapy for lung tumors in ultracentral location: the MAGELLAN trial (ARO 2021-3)

BackgroundStereotactic Body Radiotherapy (SBRT) is a standard treatment for inoperable primary and secondary lung tumors. In case of ultracentral tumor location, defined as tumor contact with vulnerable mediastinal structures such as the proximal bronchial tree (PBT) or esophagus, SBRT is associated with an increased risk for severe complications. Magnetic resonance (MR)-guided SBRT can mitigate this risk based on gated dose delivery and daily plan adaptation. The MAGELLAN trial aims to find the maximum tolerated dose (MTD) of MR-guided SBRT of ultracentral lung tumors (ULT).Patients and methodsMAGELLAN is a prospective phase I dose escalation trial. A maximum of 38 patients with primary and secondary ULT with a tumor size ≤ 5 cm will be enrolled. Ultracentral location is defined as an overlap of the planning target volume (PTV) with the PBT or esophagus. Patients are treated at a 0.35 Tesla MR-linac (MRIdian® Linac, ViewRay Inc.) employing a gating strategy and daily plan adaptation. Dose escalation starts at 10 × 5.5 Gy (biologically effective dose BED3/10: 155.83 Gy/85.25 Gy), may proceed up to 10 × 6.5 Gy (BED3/10: 205.83 Gy/107.25 Gy) and is guided by a customized time-to-event continual reassessment method (TITE CRM) with backup element, which alternately assigns patients to dose escalation and backup cohorts.DiscussionThe results of the MAGELLAN trial will guide further research and clinical implementation of MR-guided SBRT as ablative treatment of ULT. Moreover, the combination of MR-guided radiotherapy with TITE-CRM including a backup element may serve as blueprint for future radiation dose escalation studies in critical locations.Trial RegistrationRegistered at ClinicalTrials.gov: NCT04925583 on 14th June 2021.