Normal Lung Dose Research Articles

Predicting the Effect of Proton Beam Therapy Technology on Pulmonary Toxicities for Patients With Locally Advanced Lung Cancer Enrolled in the Proton Collaborative Group Prospective Clinical Trial

This study aimed to predict the probability of grade ≥2 pneumonitis or dyspnea within 12 months of receiving conventionally fractionated or mildly hypofractionated proton beam therapy for locally advanced lung cancer using machine learning. Demographic and treatment characteristics were analyzed for 965 consecutive patients treated for lung cancer with conventionally fractionated or mildly hypofractionated (2.2-3 Gy/fraction) proton beam therapy across 12 institutions. Three machine learning models (gradient boosting, additive tree, and logistic regression with lasso regularization) were implemented to predict Common Terminology Criteria for Adverse Events version 4 grade ≥2 pulmonary toxicities using double 10-fold cross-validation for parameter hyper-tuning without leak of information. Balanced accuracy and area under the curve were calculated, and 95% confidence intervals were obtained using bootstrap sampling. The median age of the patients was 70 years (range, 20-97), and they had predominantly stage IIIA or IIIB disease. They received a median dose of 60 Gy in 2 Gy/fraction, and 46.4% received concurrent chemotherapy. In total, 250 (25.9%) had grade ≥2 pulmonary toxicity. The probability of pulmonary toxicity was 0.08 for patients treated with pencil beam scanning and 0.34 for those treated with other techniques (P = 8.97e-13). Use of abdominal compression and breath hold were highly significant predictors of less toxicity (P = 2.88e-08). Higher total radiation delivered dose (P = .0182) and higher average dose to the ipsilateral lung (P = .0035) increased the likelihood of pulmonary toxicities. The gradient boosting model performed the best of the models tested, and when demographic and dosimetric features were combined, the area under the curve and balanced accuracy were 0.75 ± 0.02 and 0.67 ± 0.02, respectively. After analyzing performance versus the number of data points used for training, we observed that accuracy was limited by the number of observations. In the largest analysis of prospectively enrolled patients with lung cancer assessing pulmonary toxicities from proton therapy to date, advanced machine learning methods revealed that pencil beam scanning, abdominal compression, and lower normal lung doses can lead to significantly lower probability of developing grade ≥2 pneumonitis or dyspnea.

Correlation between AI-based CT organ features and normal lung dose in adjuvant radiotherapy following breast-conserving surgery: a multicenter prospective study

BackgroundRadiation pneumonitis (RP) is one of the common side effects after adjuvant radiotherapy in breast cancer. Irradiation dose to normal lung was related to RP. We aimed to propose an organ features based on deep learning (DL) model and to evaluate the correlation between normal lung dose and organ features.MethodsPatients with pathology-confirmed invasive breast cancer treated with adjuvant radiotherapy following breast-conserving surgery in four centers were included. From 2019 to 2020, a total of 230 patients from four nationwide centers in China were screened, of whom 208 were enrolled for DL modeling, and 22 patients from another three centers formed the external testing cohort. The subset of the internal testing cohort (n = 42) formed the internal correlation testing cohort for correlation analysis. The outline of the ipsilateral breast was marked with a lead wire before the scanning. Then, a DL model based on the High-Resolution Net was developed to detect the lead wire marker in each slice of the CT images automatically, and an in-house model was applied to segment the ipsilateral lung region. The mean and standard deviation of the distance error, the average precision, and average recall were used to measure the performance of the lead wire marker detection model. Based on these DL model results, we proposed an organ feature, and the Pearson correlation coefficient was calculated between the proposed organ feature and ipsilateral lung volume receiving 20 Gray (Gy) or more (V20).ResultsFor the lead wire marker detection model, the mean and standard deviation of the distance error, AP (5 mm) and AR (5 mm) reached 3.415 ± 4.529, 0.860, 0.883, and 4.189 ± 8.390, 0.848, 0.830 in the internal testing cohort and external testing cohort, respectively. The proposed organ feature calculated from the detected marker correlated with ipsilateral lung V20 (Pearson correlation coefficient, 0.542 with p < 0.001 in the internal correlation testing cohort and 0.554 with p = 0.008 in the external testing cohort).ConclusionsThe proposed artificial Intelligence-based CT organ feature was correlated with normal lung dose in adjuvant radiotherapy following breast-conserving surgery in patients with invasive breast cancer.Trial registrationNCT05609058 (08/11/2022).

Comparison of normal tissue doses in deep inspiration breath-hold and free breathing methods for radiotherapy of left-sided breast cancer using 4D-XCAT digital phantom.

To evaluate normal lung and heart tissue doses for treatment of left-sided breast cancer in deep inspiration breath-hold (DIBH) and free breathing (FB) as a function of breast size and diaphragm displacement using 4D-XCAT digital phantom in a simulation study. 4D-XCAT digital phantom was used to create 36 left-sided breast cancer digital phantom datasets with different breast height (BH) of 40, 50, and 60 mm, breast length (BL) of 16, 17, and 18 mm, and diaphragm excursion of 20, 25, 30, and 35 mm. For each dataset, DIBH and FB treatment plans were prepared using planning computerized radiotherapy-three dimensional (PCRT-3D) treatment planning system (TPS) with superposition computational algorithm. Dose differences in DIBH and FB plans were assessed in terms of mean lung dose (MLD), the lung volume receiving ≤20 Gy (V20), normal tissue complication probability (NTCP) of the lung, mean heart dose (MHD), and the heart volume receiving ≤30 (V30). DIBH reduced mean dose and V20 and NTCP of the lung in all cases, by up to 4.37 Gy, 7.62%, and 18.95%. Mean dose and V30 of the heart were also significantly reduced by 5.02 Gy and 8.23%. The use of DIBH for left-sided breast cancer radiotherapy offers excellent possibilities for sparing critical normal tissue without compromising radiation dose to the target.

Single-isocenter versus multiple-isocenters for multiple lung metastases: Evaluation of lung dose

Background and purposeA potential challenge in single-isocenter multi-lesion lung stereotactic body radiotherapy (SBRT) is that patient positioning is not based on each lesion individually, but on the average position of all lesions. This may lead to larger margins compared to treating with one isocenter per lesion, but increases workflow efficiency. The aim of this study was to investigate whether a single-isocenter technique leads to increased normal lung dose compared to a conventional multiple-isocenters technique. Materials and methodsA cohort of 15 NSCLC patients with two or three lesions previously treated with SBRT was subjected to treatment planning with a multiple-isocenter technique and a single-isocenter technique. For the latter, two margin approaches were evaluated: (1) identical margins for each internal target volume (ITV), assuming an average registration for all lesions in cone-beam CT (CBCT) positioning verification and (2) a smaller margin for the largest lesion, assuming an optimal registration for that lesion. For all 45 treatment plans, mean lung dose (MLD) and lungs-V20Gy were evaluated. The study was performed following RATING guidelines. ResultsThe MLD was 4.9 ± 1.9 Gy (mean ± SD) for multiple-isocenters and 5.4 ± 2.1 Gy and 5.3 ± 2.2 Gy for single-isocenter approach 1 and 2, respectively. V20Gy was 5.5 ± 3.7%, 5.5 ± 3.2% and 5.4 ± 3.3%. A median [range] increase in MLD of 11.6% [−14.9 – 26.8] was observed when comparing single-isocenter treatment plans to those with multiple isocenters. V20Gy increased by 0.2 [−3.4 – 1.3] percentage points. ConclusionA single-isocenter SBRT technique for lung patients with multiple targets results in clinically acceptable increases in normal lung dose.

Prospective Study of Surface Guided Radiation Therapy (SGRT) for Breath Hold SBRT Treatments of the Lung: Analysis of Reliability of Surface Guidance Alone for Internal Tumor Position During Breath Hold

<h3>Purpose/Objective(s)</h3> Respiratory motion management with breath hold (BH) is one technique to limit normal lung and other organ dose during SBRT treatments of the lung. Surface guidance (SGRT) has been utilized for BH in larger targets such as breast cancer, but its reliability in BH treatments of small targets has not been investigated. We report the initial results of the reliability of utilizing SGRT alone as a technique for BH during a prospective study of treatment of primary and metastatic lung tumors. <h3>Materials/Methods</h3> An IRB approved prospective study was conducted in patients (pts) with primary NSCLC or lung metastasis undergoing SBRT. Eligible pts had at least 1 cm of respiratory associated motion on free breathing 4DCT. Pts underwent planning CT with BH either in end inspiration or expiration per investigator choice. The GTV was contoured on the BH planning CT and a 5mm margin added for PTV expansion. During each SBRT treatment, pts performed BH and were aligned within tolerance based on the reference BH surface capture created from the BH planning CT. Pts underwent short-arc CBCT during BH for volumetric match of the target. Before shifts were made for target match, pts performed a BH within tolerance, then shifts were made prior to a new reference surface capture being immediately obtained during the same BH. Pts were then treated in BH based on the new reference surface with a tolerance of 3mm translations and 2 degree rotations. Treatment was stopped if pts fell outside of the predefined tolerances. Midway through treatment, pts underwent a second short arc CBCT during BH to verify the reliability of target position during BH treatment utilizing SGRT. Any subsequent shifts on target volumetric match after the second CBCT were recorded. Linear mixed models for repeated measures were used to analyze rotational and translational shift measurements. <h3>Results</h3> 13 pts and 39 SBRT fractions were treated utilizing SGRT alone for BH. All pts were treated with 54 Gy in 3 fractions. Median free breathing range of motion (4D ROM) was 1.3 cm. Mean displacements after mid-treatment CBCT were minimal in all directions as shown in Table 1. Only one observed fraction had a displacement that exceeded the 5mm PTV expansion (longitudinal shift of 0.59 cm with resulting vector shift of 0.68cm). Factors evaluated for association with shift magnitude included age, BMI, gender, tumor location, 4D ROM, and GTV and PTV size. Higher 4D ROM was associated with increased longitudinal and vector shifts (<i>P</i> = 0.019 and 0.046). <h3>Conclusion</h3> SGRT provides a reliable technique for BH SBRT treatments of the lung. Minimal target displacements on mid treatment BH CBCT were observed. Higher 4D ROM on free breathing scans correlated with larger displacements in tumor position utilizing this technique.

Use of Continuous Positive Airway Pressure (CPAP) to Limit Diaphragm Motion-A Novel Approach for Definitive Radiation Therapy for Inoperable Pleural Mesothelioma: A Pilot Study.

Simple SummaryRadiotherapy is an important part of the multimodality approach to treating malignant pleural mesothelioma. In recent studies there is a new trend to treat patients with intact lungs instead of following surgery. This treatment creates significant concerns regarding lung toxicity. We describe two methods to reduce that toxicity. One is the use of constant pulmonary airway pressure (CPAP) to inflate the lungs during treatment. The second is utilizing a novel method of planning and delivering radiotherapy called volumetric modulated arc therapy (VMAT).Malignant pleural mesothelioma (MPM) is a deadly disease and radiotherapy (RT) plays an important role in its management. Recent developments in technique have made it is possible to deliver RT to MPM in the intact lung. However, it is imperative to reduce normal lung doses. We present a pilot study examining the use of CPAP and VMAT radiotherapy to reduce toxicity when treating MPM, involving three consecutive patients with MPM, not amenable to surgery, who were treated according to Helsinki committee approval. Patients were simulated using four-dimentional CT simulation with the assistance of CPAP lung inflation, then were treated using both IMRT and VMAT techniques. Radiation lung dose was optimized based on accepted lung dose constraints. Patients were followed for toxicity as well as local control and survival. Results: Three patients were treated with CPAP-based IMRT treatment. These patients tolerated the treatment and DVH constraints were able to be met. The comparison plans among the four VMAT arcs and the IMRT static field treatment were able to accomplish the treatment planning objectives without significant advantages with either technique. The treatment combined with CPAP reduced the normal lung dose in MPM patients with intact lungs. This technique is worthy of further investigation.

A treatment planning study comparison between supine and prone position for different lung tumour locations using CyberKnife TPS

AbstractAim:CyberKnife is the most advanced form of stereotactic body radiotherapy (SBRT) system that uses a robotic arm to deliver highly focused beams of radiation; however, a limitation is that it only irradiates from ceiling to floor direction. In patients with posterior lungs tumour who are positioned supine, normal lung tissue may suffer undesirable radiation injuries. This study compares the treatment planning between the prone set-up and the supine set-up for lung cancer in CyberKnife SBRT to decrease normal lung dose to avoid radiation side effects.Materials and methods:A human phantom was used to generate 108 plans (54 for prone and 54 for supine) using the CyberKnife planning platform. The supine and prone plans were compared in terms of the dosimetric characteristics, delivery efficiency and plan efficiency.Results:For posterior targets, the area of low-dose exposure to normal lungs was smaller in the prone set-up than in the supine set-up. V10 of the lungs was 7·53% and 10·47% (p &lt; 0·001) in the anterior region, and 10·78% and 8·03% (p &lt; 0·001) in the posterior region in the supine and prone set-up plans, respectively.Conclusions:The comparison between the prone set-up and the supine set-up was investigated with regard to target coverage and dose to organs at risk. Our results may be deployed in CyberKnife treatment planning to monitor normal tissue dose by considering patient positioning. This may assist in the design of better treatment plans and prevention of symptomatic radiation pneumonitis in lung cancer patients.

Lung dose reduction in patients with stage III non-small-cell lung cancer using software that estimates patient-specific dose reduction feasibility.

In radiotherapy, the dose to organs-at-risk must be kept as low as possible to preserve their function. We aimed to determine the acceptable f-value upper bound of the Feasibility DVH in the PlanIQ software to achieve dose reduction to the normal lung in patients with stage III non-small cell lung cancer. By using the Feasibility DVH, the f-values corresponding to the pulmonary dosimetric parameters of each treatment plan for 11 patients were calculated. The acceptable f-value upper bound was defined as the value that added one standard deviation of the f-value to the mean. Additionally, the treatment plan for additional fourteen patients was designed to evaluate the effectiveness of the acceptable f-value upper bound for the normal lung dose reduction. The value beyond the acceptable f-value upper bound was judged as inadequate dose reduction. The acceptable f-value upper bound was different for dosimetric parameters (range, 0.22-0.26). These values were<0.5, which is typically used as the acceptable f-value upper bound. Evaluation by the treatment plan of fourteen patients detected that the f-value of the normal lung of five patients exceeded the acceptable f-value upper bound, and the replanning was able to reduce the dose of the normal lung. We could efficiently reduce the normal-lung dose using the acceptable f-value upper bound calculated in this study and provide an effective acceptable f-value upper bound of the normal lung dose in the lung cancer radiotherapy.

Robust Treatment Planning in Intrafraction Motion Using TomoDirect™ Intensity-modulated Radiotherapy for Breast Cancer.

To evaluate the robustness of radiotherapy treatment planning optimization for respiratory-moving breast cancer using fixed-angle beams planning TomoDirect™ intensity-modulated radiotherapy (IMRT). A minimax optimisation algorithm was applied to 10 breast cancer patients. Two sets of treatment plans with or without robust techniques were prepared considering anterior-posterior and head-tail movements due to respiration. Parameters were compared between treatment plans: 95% planned target volume (PTV) dose, conformal index and homogeneity index (HI), and organs at risk (OAR) parameters including the lung volume receiving 20 Gy or more (V20) and 5 Gy (V5). Robust planning significantly improved parameters of 95% PTV dose and HI, without deteriorating V20 or V5 in the anterior-posterior movement, while it slightly improved 95% PTV and slightly deteriorated V20 in the head-tail movement. Robust treatment planning improves coverage of targets moving because of respiration in the treatment of breast cancer using TomoDirect; however, normal lung doses should be cautiously evaluated on a case-by-case basis.

Optimal Management of Radiation Pneumonitis: Preliminary Findings of an International Delphi Consensus Study

Radiation pneumonitis (RP) is a dose-limiting toxicity for patients undergoing radiotherapy (RT) and systemic therapy for lung cancer; however, the optimal practice for diagnosis, management and follow-up remains unclear. We sought to establish expert consensus recommendations for RP management. Following literature review on RP, 9 open-ended questions related to knowledge, risk-reduction, diagnosis and treatment were generated for this first round of a consensus-building Delphi process. International leaders in multidisciplinary thoracic oncology were invited to participate (n = 31). Key statements regarding RP diagnosis and management were generated from responses to produce statements for Round 2. Participants will be solicited regarding agreement/disagreement with statements using a 5-point Likert scale. Subsequent rounds will seek consensus in areas that remain unresolved. For Round 1, a 74% response rate (n = 23; 12 radiation oncologists, 5 clinical oncologists, 6 respirologists) was achieved. Eighty-three percent of respondents were not aware of any guidelines for management of RP and 17% used local guidelines or expert review articles. Clinical history, exam and lab criteria (13 respondents) and imaging (15 respondents) were cited as used for diagnosis, and RTOG (9 respondents) and CTCAE grading (14 respondents) for assessment. Radiation-specific factors predictive of RP included irradiated lung volume (especially V20), dose, RT technique and location. The majority of clinical and radiation oncologists used motion management, image guidance and IMRT planning to achieve dosimetric constraints and minimize normal lung dose. Systemic therapy-related RP predictive factors included adjuvant or concurrent chemotherapy, immunotherapy (IO), and use of other pulmonotoxic medications. Patient-related predictive factors included lung function, autoimmune disease, age, performance status and smoking status. Majority of clinicians use risk stratification of patients in order to mitigate RP. Respondents uniformly agreed that steroid therapy is the mainstay of treatment for moderate to severe RP, with variability in the dosing and tapers used. A multidisciplinary management approach was favored by all, including radiation and medical oncologists, respirologists, thoracic radiologists and/or infectious disease or rheumatology specialists if indicated. The majority believe that IO will add complexity in identifying RP. Regarding additional measures to prevent RP in IO patients, respondents were split, with 50% taking additional measures and 50% not, though majority favored monitoring by oncologists during IO cycles and counseling patients on increased RP risk. Responses from international thoracic oncology experts highlight areas lacking consensus in the diagnosis and management of RP. These data will inform the next round of Delphi questions, with an aim of reaching consensus on this common issue.

Single-Isocenter/Multi-Lesion Synchronous Lung Stereotactic Body Radiation Therapy (SBRT): Plan Quality, Treatment Efficiency and Clinical Outcomes

Patients with multiple primary or metastatic lung lesions may not well tolerate relatively longer SBRT treatments due to distress or shortness of breath, with traditional treatment planning and delivery with individual isocenter per lesion. Treating lesions synchronously with a single-isocenter volumetric modulated arc therapy (VMAT) plan with flattening filter free (FFF) beam will decrease treatment time and improve patient comfort. We report dosimetry, treatment efficiency and early clinical outcomes of oligometastases (< 5 lesions) lung cancer patients who underwent synchronous single-isocenter/multiple-lesions VMAT lung SBRT. Fourteen patients with multiple peripherally located non-small-cell-lung cancer (NSCLC) lesions (two n = 12, three n = 1, five n = 1, total 32 lesions) were treated synchronously with highly conformal single-isocenter non-coplanar VMAT-SBRT plan (bilateral lesions n = 6, right lesions n = 5, left lesions n = 3). Single-isocenter was placed between or in the middle of all lesions. Doses were 54 Gy/50 Gy in 3/5 fractions prescribed to 70-80% isodose line. Plans were generated with Acuros-based algorithm and 6MV-FFF beam following RTOG criteria. Plan quality and delivery efficiency were reported. Outcomes evaluated include local control rates, radiation pneumonitis and rib toxicity. Kaplan-Meier (KM) estimates of time-to-local failure were investigated. Median follow-up time was 5 ± 5 months (range 1 to 15 months). Mean isocenter to tumor distance was 5.6 ± 1.9 cm. Mean combined planning target volume (PTV) was 38.7 ± 22.7 cc. All plans were accepted by treating physicians and met RTOG criteria for target coverage and organs at risk (OAR) dose. Average values of conformity index, gradient index, maximum dose at 2 cm away from the PTV and normal lung V20 were 1.05 ± 0.1, 5.1 ± 0.8, 50.1 ± 5.2% and 6.4 ± 3.1%, respectively. All OAR doses were well below RTOG criteria. Additionally, normal lung V10, V5 and mean lung dose were 18.2%, 31.0 % and 5.4 Gy, on average, respectively. Average beam on time was 3.4 ± 1.4 min. One patient died before follow up and one was lost to follow up. Of twelve patients, eleven achieved complete response to treatment with one lesion of one patient progressing. KM estimated 1-year actuarial tumor local control rate was 100%; however, 50% of the patients developed distant metastases. During the follow-up period, no patient had adverse pulmonary effects, developed grade+2 pneumonitis or had chest wall pain/rib fracture. However, four patients developed radiographic changes that were asymptomatic. Synchronous SBRT treatment to oligometastases lung lesions was fast, effective and safe, with promising early clinical outcomes in terms of local control rates and no adverse side effects to lung or ribs. Although six patients had distant failure, the local control of treated lesions could preserve the patient’s quality of life or delay chemotherapy treatment. Longer follow up of these patients is warranted.

Potential reduction of lung dose via VMAT with jaw tracking in the treatment of single-isocenter/two-lesion lung SBRT.

Purpose/objectivesDue to higher radiosensitivity, non‐target normal tissue dose is a major concern in stereotactic body radiation therapy (SBRT) treatment. The aim of this report was to estimate the dosimetric impact, specifically the reduction of normal lung dose in the treatment of single‐isocenter/two‐lesion lung SBRT via volumetric modulated arc therapy with jaw tracking (JT‐VMAT).Materials/methodsTwelve patients with two peripherally located early‐stage non‐small‐cell‐lung cancer (NSCLC) lung lesions underwent single‐isocenter highly conformal non‐coplanar JT‐VMAT SBRT treatment in our institution. The mean isocenter to tumors distance was 5.6 ± 1.9 (range 4.3–9.5) cm. The mean combined planning target volume (PTV) was 38.7 ± 22.7 (range 5.0–80.9) cc. A single isocenter was placed between the two lesions. Doses were 54 and 50 Gy in three and five fractions, respectively. Plans were optimized in Eclipse with AcurosXB algorithm utilizing jaw tracking options for the Truebeam with a 6 MV‐FFF beam and standard 120 leaf millennium multi‐leaf collimators. For comparison, the JT‐VMAT plans were retrospectively re‐computed utilizing identical beam geometry, objectives, and planning parameters, but without jaw tracking (no JT‐VMAT). Both plans were normalized to receive the same target coverage. The conformity and heterogeneity indices, intermediate‐dose spillage [D2cm, R50, Gradient Index (GI), Gradient Distance (GD)], organs at risks (OAR) doses including normal lung as well as modulation factor (MF) were compared for both plans.ResultsFor similar target coverage, GI, R50, GD, as well as the normal lung V5, V10, V20, mean lung dose (MLD), and maximum dose received by 1000 cc of lungs were statistically significant. Normal lung doses were reduced by 8%–11% with JT‐VMAT. Normal lung dose increased as a function of tumor distance from isocenter. For the other OAR, up to 1%–16% reduction of non‐target doses were observed with JT‐VMAT. The MF and beam‐on time were similar for both plans, however, MF increased as a function of tumors distance, consequently, delivering higher dose to normal lungs.ConclusionUtilizing jaw tracking options during optimization for single‐isocenter/two‐lesion lung SBRT VMAT plans reduced doses to the normal lung and other OAR, reduced intermediate‐dose spillage and provided superior/similar target coverage. Application of jaw tracking did not affect delivery efficiency and provided excellent plan quality with similar MF and beam‐on time. Jaw tracking is recommended for future clinical SBRT plan optimization.

First-in-Human Clinical Experience with Real-Time Tumor Targeting Via MLC Tracking for Stereotactic Radiation Therapy of Lung Cancer

MLC tracking is an emerging technology to improve tumor targeting and reduce normal tissue irradiation during radiotherapy. The purpose of this work is to present the early clinical experience from the first-in-human trial of real-time tumor targeting via MLC tracking for stereotactic ablative body radiotherapy (SABR) of lung cancer. Twelve stage 1 lung cancer or lung metastases patients have been recruited into an ethics approved MLC tracking clinical trial (NCT02514512). Each patient has three electromagnetic beacons (Calypso) inserted into the lung surrounding the tumor. An MLC tracking SABR plan was generated with planning target volume (PTV) expanded 5mm from end-exhale tumor volume (GTV). For comparison a conventional motion-encompassing SABR plan was generated with PTV expanded 5mm from a 4DCT-derived internal target volume. Treatment was delivered using a standard linear accelerator using in-house developed software to continuously adapt the MLC motion based on the Calypso beacons’ movement. Tumor motion, treated volume, and reconstructed delivered dose were compared between MLC tracking and conventional motion-encompassing treatment planning. All 46 fractions from the twelve patients have been treated successfully with MLC tracking. The MLC tracking PTV for all patients has been smaller than with ITV based planning (range 12% to 41% reduction, or 2 to 18 cm3 with MLC tracking). Subsequent reductions in normal lung dose were observed. Mean lung dose reduced by up to 30% and on average by 19% (i.e., from 280 cGy to 225 cGy) with MLC tracking compared to ITV-based planning. Tumor motion was seen to vary in motion range during treatment, between fractions and from the planning 4DCT; significantly, larger motion was observed during treatment that exceeded standard PTV boundaries. Reconstruction of delivered treatments confirmed the accurate delivery of MLC tracking, with 100% prescribed dose delivered to the GTV for each of the 46 fractions. The first treatments with MLC tracking have been successfully performed in twelve lung cancer patients. Reductions in treated volumes were observed, which translated to reductions in delivered lung dose.

Outcomes of Real-Time MRI-guided Lung Stereotactic Body Radiation Therapy

Lung stereotactic body radiation therapy (SBRT) is an effective therapy that provides excellent local control for small primary and/or metastatic lung tumors. We report our experience using real-time MRI-guidance with respiratory breath hold gating for delivery of lung SBRT. Patients with primary or metastatic lung tumors ≤5cm were eligible for treatment with MRI-guided SBRT. Patients underwent simulation and treatment on a Cobalt-60 MRI-guided treatment planning system, with max inhale breath hold used to minimize normal lung dose. All patients underwent 4D-CT simulation as well. Gross tumor to PTV expansions were 3mm, with gross tumor tracked in real-time during treatment and the PTV, or similar numeric expansion, used as a boundary structure for gating. Thirteen of fifteen tumors were treated with 50 Gy in 5 fractions, with the remaining two treated with 45 Gy in 5 fractions and 40 Gy in 5 fractions. Constraints for radiation therapy were similar to RTOG 0813. For comparison, the 4D-CT was used to create an ITV, which was itself expanded 5mm to PTV as per institutional practice. The study population consisted of fourteen patients with a total of fifteen treated tumors. Eleven of fourteen patients had primary non-small cell lung cancer, while the remaining three had metastatic lung tumors (nasopharygeal adenoid cystic carcinoma, breast adenocarcinoma, and tonsil squamous cell carcinoma). Nine of the fourteen patients were female, with a median age of 69.5 years (range 60-79). The median follow-up at this time is 13.7 months (range 1.6-35.9 months). The median PTV volume using respiratory gating with MRI-guidance was 16.5cc (range 2.8-58.5cc), compared to a median PTV volume of 43.6cc (range 8.2-136.4cc, p= 0.01) when using an ITV to account for respiratory motion. Median Lung-PTV volume using respiratory gating with MRI-guidance was 4746.9cc (range 2742.5-6563.5cc) compared to 3967.8cc (range 2255.8-5190.0cc, p = 0.02) when using an ITV. Analysis of > 800 minutes of cine images shows patients were coached into repeatable tumor positioning (< 2 mm) for a median breathhold of 29 seconds, with a median duty cycle of 53%. No treatment-related toxicities were noted. Only one of the fifteen treated tumors, a right hilar metastasis from right tonsil primary, recurred at 5 months after treatment. This tumor was seen to have responded to therapy on initial post-treatment imaging; however, subsequent imaging identified local failure at the right hilum as well as progression of systemic disease elsewhere. Of note, this tumor was treated with 40 Gy in 5 fractions. MRI-guided SBRT to the lung is well-tolerated by patients and provides excellent local control similar to historic controls. Respiratory gating utilizing real-time tumor visualization allows for smaller PTV volumes and greater sparing of normal lung.

Estimating lung, breast, and effective dose from low-dose lung cancer screening CT exams with tube current modulation across a range of patient sizes.

The purpose of this study was to estimate the radiation dose to the lung and breast as well as the effective dose from tube current modulated (TCM) lung cancer screening (LCS) scans across a range of patient sizes. Monte Carlo (MC) methods were used to calculate lung, breast, and effective doses from a low-dose LCS protocol for a 64-slice CT that used TCM. Scanning parameters were from the protocols published by AAPM's Alliance for Quality CT. To determine lung, breast, and effective doses from lung cancer screening, eight GSF/ICRP voxelized phantom models with all radiosensitive organs identified were used to estimate lung, breast, and effective doses. Additionally, to extend the limited size range provided by the GSF/ICRP phantom models, 30 voxelized patient models of thoracic anatomy were generated from LCS patient data. For these patient models, lung and breast were semi-automatically segmented. TCM schemes for each of the GSF/ICRP phantom models were generated using a validated method wherein tissue attenuation and scanner limitations were used to determine the TCM output as a function of table position and source angle. TCM schemes for voxelized patient models were extracted from the raw projection data. The water equivalent diameter, Dw, was used as the patient size descriptor. Dw was estimated for the GSF/ICRP models. For the thoracic patient models, Dw was extracted from the DICOM header of the CT localizer radiograph. MC simulations were performed using the TCM scheme for each model. Absolute organ doses were tallied and effective doses were calculated using ICRP 103 tissue weighting factors for the GSF/ICRP models. Metrics of scanner radiation output were determined based on each model's TCM scheme, including CTDIvol , dose length product (DLP), and CTDIvol, Low Att , a previously described regional metric of scanner output covering most of the lungs and breast. All lung and breast doses values were normalized by scan-specific CTDIvol and CTDIvol, Low Att . Effective doses were normalized by scan-specific CTDIvol and DLP. Absolute and normalized doses were reported as a function of Dw. Lung doses normalized by CTDIvol, Low Att were modeled as an exponential relationship with respect to Dw with coefficients of determination (R2 ) of 0.80. Breast dose normalized by CTDIvol, Low Att was modeled with an exponential relationship to Dw with an R2 of 0.23. For all eight GSF/ICRP phantom models, the effective dose using TCM protocols was below 1.6 mSv. Effective doses showed some size dependence but when normalized by DLP demonstrated a constant behavior. Lung, breast, and effective doses from LCS CT exams with TCM were estimated with respect to patient size. Normalized lung dose can be reasonably estimated with a measure of a patient size such as Dw and regional metric of CTDIvol covering the thorax such as CTDIvol, Low Att , while normalized breast dose can also be estimated with a regional metric of CTDIvol but with a larger degree of variability than observed for lung. Effective dose normalized by DLP can be estimated with a constant multiplier.

Robust optimization in lung treatment plans accounting for geometric uncertainty.

Robust optimization generates scenario‐based plans by a minimax optimization method to find optimal scenario for the trade‐off between target coverage robustness and organ‐at‐risk (OAR) sparing. In this study, 20 lung cancer patients with tumors located at various anatomical regions within the lungs were selected and robust optimization photon treatment plans including intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) plans were generated. The plan robustness was analyzed using perturbed doses with setup error boundary of ±3 mm in anterior/posterior (AP), ±3 mm in left/right (LR), and ±5 mm in inferior/superior (IS) directions from isocenter. Perturbed doses for D99, D98, and D95 were computed from six shifted isocenter plans to evaluate plan robustness. Dosimetric study was performed to compare the internal target volume‐based robust optimization plans (ITV‐IMRT and ITV‐VMAT) and conventional PTV margin‐based plans (PTV‐IMRT and PTV‐VMAT). The dosimetric comparison parameters were: ITV target mean dose (Dmean), R95(D95/Dprescription), Paddick's conformity index (CI), homogeneity index (HI), monitor unit (MU), and OAR doses including lung (Dmean, V20 Gy and V15 Gy), chest wall, heart, esophagus, and maximum cord doses. A comparison of optimization results showed the robust optimization plan had better ITV dose coverage, better CI, worse HI, and lower OAR doses than conventional PTV margin‐based plans. Plan robustness evaluation showed that the perturbed doses of D99, D98, and D95 were all satisfied at least 99% of the ITV to received 95% of prescription doses. It was also observed that PTV margin‐based plans had higher MU than robust optimization plans. The results also showed robust optimization can generate plans that offer increased OAR sparing, especially for normal lungs and OARs near or abutting the target. Weak correlation was found between normal lung dose and target size, and no other correlation was observed in this study.

Normal lung sparing Tomotherapy technique in stage III lung cancer

PurposeRadiation pneumonitis (RP) has been a challenging obstacle in treating stage III lung cancer patients. Beam angle optimization (BAO) technique for Tomotherapy was developed to reduce the normal lung dose for stage III non-small cell lung cancer (NSCLC). Comparative analyses on plan quality by 3 different Intensity-modulated radiation therapy (IMRT) methods with BAO were done.Materials and methodsTen consecutive stage IIIB NSCLC patients receiving linac-based static IMRT (L-IMRT) with total 66 Gy in 33 fractions to the PTV were selected. Two additional Tomotherapy-based IMRT plans (helical beam (TH-IMRT) and static beam (TD-IMRT)) were generated on each patient. To reduce the normal lung dose, Beam angles were optimized by using complete and directional block functions in Tomotherapy based on knowledge based statistical analysis. Plan quality was compared with target coverage, normal organ sparing capability, and normal tissue complication probability (NTCP). Actual beam delivery times and risk of RP related with planning target volume (PTV) were also evaluated.ResultsThe best PTV coverage measured by conformity index and homogeneity index was achievable by TH-IMRT (0.82 and 1.06), followed by TD-IMRT (0.81 and 1.07) and L-IMRT (0.75 and 1.08). Mean lung dose was the lowest in TH-IMRT plan followed by TD-IMRT and L-IMRT, all of which were ≤20 Gy. TH-IMRT plan could significantly lower the lung volumes receiving low to medium dose levels: V5~30 when compared to L-IMRT plan; and V5~20 when compared to TD-IMRT plan, respectively. TD-IMRT plan was significantly better than L-IMRT with respects to V20 and V30 and there was no significant difference with respect to V40 among three plans. The NTCP of the lung was the lowest in TH-IMRT plan, followed by TD-IMRT and L-IMRT (6.42% vs. 6.53% vs. 8.11%). Beam delivery time was the shortest in TD-IMRT plan followed by L-IMRT. As PTV length increased, NTCP and Mean lung dose proportionally increased significantly in all three plans.ConclusionAdvantageous profiles by TH-IMRT could be achieved by BAO by complete and directional block functions. Current observation could help radiation oncologists to make wise selection of IMRT method for stage IIIB NSCLC.

MA13.02 First-In-Human Clinical Experience with Real-Time Tumor Targeting via MLC Tracking for Stereotactic Radiotherapy of Lung Cancer

MLC tracking is an emerging technology to improve tumor targeting and reduce normal tissue irradiation during radiotherapy. The purpose of this work is to present the early clinical experience from the first-in-human trial of real-time tumor targeting via MLC tracking for stereotactic ablative body radiotherapy (SABR) of lung cancer. Full ethics approval through an Australian ethics board has been received for recruitment of 20 patients with stage 1 lung cancer or lung metastases into the MLC tracking clinical trial (NCT02514512). To date, seven recruited patients have each had three electromagnetic beacons inserted near the tumor. An MLC tracking SABR plan was generated with planning target volume (PTV) expanded 5mm from end-exhale tumor volume (GTV). For comparison a conventional motion-encompassing SABR plan was generated with PTV expanded 5mm from a 4DCT-derived internal target volume. Treatment was delivered using a standard linear accelerator using in-house developed software to continuously adapt the MLC motion based on the Calypso beacons’ movement. Tumor motion, treated volume and reconstructed delivered dose were compared between MLC tracking and conventional motion-encompassing treatment planning. All seven patients have been treated successfully with MLC tracking (29 successful fractions). The MLC tracking PTV for all patients has been smaller than with ITV based planning (range 12% to 41% reduction, or 2 to 18 cm3 with MLC tracking). Subsequent reductions in normal lung dose were observed. Tumor motion was seen to vary in motion range from the planning 4DCT during treatment; significantly, larger motion was observed during treatment that exceeded standard PTV boundaries. Reconstruction of delivered treatments confirmed the accurate delivery of MLC tracking, with 100% prescribed dose delivered to the GTV. The first treatments with MLC tracking have been successfully performed in seven lung cancer patients. Reductions in treated volumes were observed, which translated to reductions in delivered lung dose.

Dosimetric analysis of rib interference of the CTV during interstitial brachytherapy of lung tumors.

PurposeIn interstitial brachytherapy for lung tumors, the placement and alignment of the source needles are influenced by the ribs, which can affect the dose distribution. This study evaluated the change in dose to the target by comparing the dose between the actual interstitial brachytherapy plan (AIBP, what is deliverable due to anatomic constraints), and the virtual interstitial brachytherapy plan (VIBP, pretreatment-modified dose distribution).Material and methodsAIBPs and VIBPs were designed for 20 lung tumors. The VIBP was designed with uniform spacing between needles, regardless of the presence of ribs. The prescription dose was 30 Gy. The percentage of normal ipsilateral lung volume that received a dose ≥ 5 Gy (V5), conformity index (COIN), incremental dose percentage (IDP) to the target, and the dose covering 95% (D95) of the clinical target volume (CTV) were calculated.ResultsThe V5 of the VIBPs was significantly smaller than that of the AIBPs (p < 0.01). The mean COIN value was 0.41 ± 0.12 for the AIBPs, which was significantly smaller than the value 0.54 ± 0.12 for the VIBPs (p < 0.01). The D95 of CTV in VIBP-adjusted was greater than that in AIBPs (p < 0.01). The mean IDP was 44% ± 40%. The Dmax of the ribs was 20.16 Gy ± 15.76 Gy in AIBPs, and 18.57 Gy ± 15.14 Gy in VIBPs, which was not significantly different (p > 0.05).ConclusionsThe regular geometric alignment of needles is important for increasing the target dose and limiting the normal lung dose in interstitial brachytherapy for thoracic tumors. Thus, we recommend that radiation oncologists attempt to achieve the regular alignment of needles during implantation.

Dosimetric comparison between proton beam therapy and photon radiation therapy for locally advanced non-small cell lung cancer.

To assess the feasibility of proton beam therapy for the patients with locally advanced non-small lung cancer. The dosimetry was analyzed retrospectively to calculate the doses to organs at risk, such as the lung, heart, esophagus and spinal cord. A dosimetric comparison between proton beam therapy and dummy photon radiotherapy (three-dimensional conformal radiotherapy) plans was performed. Dummy intensity-modulated radiotherapy plans were also generated for the patients for whom curative three-dimensional conformal radiotherapy plans could not be generated. Overall, 33 patients with stage III non-small cell lung cancer were treated with proton beam therapy between December 2011 and August 2014. The median age of the eligible patients was 67 years (range: 44-87 years). All the patients were treated with chemotherapy consisting of cisplatin/vinorelbine or carboplatin. The median prescribed dose was 60 GyE (range: 60-66 GyE). The mean normal lung V20 GyE was 23.6% (range: 14.9-32%), and the mean normal lung dose was 11.9 GyE (range: 6.0-19 GyE). The mean esophageal V50 GyE was 25.5% (range: 0.01-63.6%), the mean heart V40 GyE was 13.4% (range: 1.4-29.3%) and the mean maximum spinal cord dose was 40.7 GyE (range: 22.9-48 GyE). Based on dummy three-dimensional conformal radiotherapy planning, 12 patients were regarded as not being suitable for radical thoracic three-dimensional conformal radiotherapy. All the dose parameters of proton beam therapy, except for the esophageal dose, were lower than those for the dummy three-dimensional conformal radiotherapy plans. In comparison to the intensity-modulated radiotherapy plan, proton beam therapy also achieved dose reduction in the normal lung. None of the patients experienced grade 4 or worse non-hematological toxicities. Proton beam therapy for patients with stage III non-small cell lung cancer was feasible and was superior to three-dimensional conformal radiotherapy for several dosimetric parameters.