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Purpose: Cardiac substructure dose metrics are more strongly linked to late cardiac morbidities than to whole-heart metrics. Magnetic resonance (MR)-guided radiation therapy (MRgRT) enables substructure visualization during daily localization, allowing potential for enhanced cardiac sparing. We extend a publicly available state-of-the-art deep learning framework, "No New" U-Net, to incorporate self-distillation (nnU-Net.wSD) for substructure segmentation for MRgRT., Methods and Materials: Eighteen (institute A) patients who underwent thoracic or abdominal radiation therapy on a 0.35 T MR-guided linear accelerator were retrospectively evaluated. On each image, 1 of 2 radiation oncologists delineated reference contours of 12 cardiac substructures (chambers, great vessels, and coronary arteries) used to train (n = 10), validate (n = 3), and test (n = 5) nnU-Net.wSD by leveraging a teacher-student network and comparing it to standard 3-dimensional U-Net. The impact of using simulation data or including 3 to 4 daily images for augmentation during training was evaluated for nnU-Net.wSD. Geometric metrics (Dice similarity coefficient, mean distance to agreement, and 95% Hausdorff distance), visual inspection, and clinical dose-volume histograms were evaluated. To determine generalizability, institute A's model was tested on an unlabeled data set from institute B (n = 22) and evaluated via consensus scoring and volume comparisons., Results: nnU-Net.wSD yielded a Dice similarity coefficient (reported mean ± SD) of 0.65 ± 0.25 across the 12 substructures (chambers, 0.85 ± 0.05; great vessels, 0.67 ± 0.19; and coronary arteries, 0.33 ± 0.16; mean distance to agreement, <3 mm; mean 95% Hausdorff distance, <9 mm) while outperforming the 3-dimensional U-Net (0.583 ± 0.28; P <.01). Leveraging fractionated data for augmentation improved over a single MR simulation time point (0.579 ± 0.29; P <.01). Predicted contours yielded dose-volume histograms that closely matched those of the clinical treatment plans where mean and maximum (ie, dose to 0.03 cc) doses deviated by 0.32 ± 0.5 Gy and 1.42 ± 2.6 Gy, respectively. There were no statistically significant differences between institute A and B volumes (P >.05) for 11 of 12 substructures, with larger volumes requiring minor changes and coronary arteries exhibiting more variability., Conclusions: This work is a critical step toward rapid and reliable cardiac substructure segmentation to improve cardiac sparing in low-field MRgRT., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: We sought to evaluate the toxicity and efficacy of stereotactic body radiation therapy (SBRT) for ultracentral thoracic tumors at our institution., Methods and Materials: Patients with ultracentral lung tumors or nodes, defined as having the planning target volume (PTV) overlapping or abutting the central bronchial tree and/or esophagus, treated at our institution with SBRT between 2009 and 2019 were retrospectively reviewed. All SBRT plans were generated with the goal of creating homogenous dose distributions. The primary endpoint was incidence of SBRT-related grade ≥3 toxicity, defined using the Common Terminology Criteria for Adverse Events (V5.0). Secondary endpoints included local failure (LF), progression-free survival (PFS), and overall survival. Competing risk analysis was used to estimate incidence and identify predictors of severe toxicity and LF, while the Kaplan-Meier method was used to estimate PFS and OS., Results: A total of 154 patients receiving 162 ultracentral courses of SBRT were included. The most common prescription was 50 Gy in 5 fractions (42%), with doses ranging from 30 to 55 Gy in 5 fractions (BED10 range, 48-115 Gy). The incidence of severe toxicity was 9.4% at 3 years. The most common severe toxicity was pneumonitis (n = 4). There was 1 possible treatment-related death from pneumonitis/pneumonia. Predictors of severe toxicity included increased PTV size, decreased PTV V95%, lung V5 Gy, and lung V20 Gy. The incidence of LF was 14% at 3 years. Predictors of LF included younger age and greater volume of overlap between the PTV and esophagus. The median PFS was 8.8 months, while the median overall survival was 44.0 months., Conclusions: In the largest case series of ultracentral thoracic SBRT to date, homogenously prescribed SBRT was associated with relatively low rates of severe toxicity and LF. Predictors of toxicity should be interpreted in the context of the heterogeneity in toxicities observed., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the application of equivalent uniform dose (EUD) in intensity-modulated rotational radiotherapy and to explore optimization methods for improving the quality of modulated treatment plans., Methods: The impact of the parameter a in the EUD formula on the characteristics of the EUD curve was analyzed using Python. Thirty cases of head and neck tumors, thoracic tumors, and pelvic tumors were randomly selected for treatment planning. Dose optimization for the target area and organs at risk were performed using a physics-based optimization approach or an optimization approach that combines physical constraints with the EUD function. The dose distribution and compliance with constraints of the two groups of plans were compared, while also observing the effect of different values of a on the planning outcomes., Results: The impact of the value of a on the changes in EUD curve characteristics was consistent with its impact on the results of EUD plan optimization. When -15≤ a ≤-5, the dose distribution in the target area was more uniform; when 1≤ a ≤7, the effect on the uniform dose and low-dose regions in organs at risk was more noticeable; when 10≤ a ≤30, the effect of constraining the high-dose regions in organs at risk was more pronounced, with the EUD for the target area and organs at risk exhibiting different expressions under different a values. The study also found that the target dose distribution and the protection of organs at risk in the EUD optimization group were better than those in the physical optimization group only., Conclusion: The a -value has a significant impact on the, the dose distribution in the target area and the organ at risk, providing a reference for the setting of a -value while using EUD to optimize the intensity modulation plan. The using of EUD optimization method can not only achieve excellent dose distribution in the target area, but also significantly reduce the normal tissue dose and the probability of complications, which has certain clinical application value.

Stereotactic body radiation therapy (SBRT) and hypofractionation using pencil-beam scanning (PBS) proton therapy (PBSPT) is an attractive option for thoracic malignancies. Combining the advantages of target coverage conformity and critical organ sparing from both PBSPT and SBRT, this new delivery technique has great potential to improve the therapeutic ratio, particularly for tumors near critical organs. Safe and effective implementation of PBSPT SBRT/hypofractionation to treat thoracic malignancies is more challenging than the conventionally fractionated PBSPT because of concerns of amplified uncertainties at the larger dose per fraction. The NRG Oncology and Particle Therapy Cooperative Group Thoracic Subcommittee surveyed proton centers in the United States to identify practice patterns of thoracic PBSPT SBRT/hypofractionation. From these patterns, we present recommendations for future technical development of proton SBRT/hypofractionation for thoracic treatment. Among other points, the recommendations highlight the need for volumetric image guidance and multiple computed tomography-based robust optimization and robustness tools to minimize further the effect of uncertainties associated with respiratory motion. Advances in direct motion analysis techniques are urgently needed to supplement current motion management techniques., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Purpose: Concerns over chest wall toxicity has led to debates on treating tumors adjacent to the chest wall with single-fraction stereotactic ablative radiotherapy (SABR). We performed a secondary analysis of patients treated on the prospective iSABR trial to determine the incidence and grade of chest wall pain and modeled dose-response to guide radiation planning and estimate risk., Materials and Methods: This analysis included 99 tumors in 92 patients that were treated with 25 Gy in one fraction on the iSABR trial which individualized dose by tumor size and location. Toxicity events were prospectively collected and graded based on the CTCAE version 4. Dose-response modeling was performed using a logistic model with maximum likelihood method utilized for parameter fitting., Results: There were 22 grade 1 or higher chest wall pain events, including five grade 2 events and zero grade 3 or higher events. The volume receiving at least 11 Gy (V 11Gy ) and the minimum dose to the hottest 2 cc (D 2cc ) were most highly correlated with toxicity. When dichotomized by an estimated incidence of ≥ 20 % toxicity, the D 2cc  > 17 Gy (36.6 % vs. 3.7 %, p < 0.01) and V 11Gy  > 28 cc (40.0 % vs. 8.1 %, p < 0.01) constraints were predictive of chest wall pain, including among a subset of patients with tumors abutting or adjacent to the chest wall., Conclusion: For small, peripheral tumors, single-fraction SABR is associated with modest rates of low-grade chest wall pain. Proximity to the chest wall may not contraindicate single fractionation when using highly conformal, image-guided techniques with sharp dose gradients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: B.L., Y.F.W., S.C., J.F., S.J., P.D., H.G., V.M., S.E., H.S., and A.L.C. report no disclosures. L.S. reports US patent: 16/809427. D.P. reports disclosures including a grant with RefleXion Medical Research. H.T. reports a contract with the Global Center for Biomedical Science and Engineering at Hokkaido University. M.F.G. reports disclosures including grants with Varian Medical Systems and stock holdings with Roche. M.Diehnreports disclosures including research support from AstraZeneca and Varian Medical Systems, royalties for patent licenses from Roche and Foresight Diagnostics, consulting fees from AstraZeneca, Boehringer Ingelheim, Genentech, Gritstone Bio, Illumina, and Regeneron, honoraria from Bristol Myers Squibb and Novartis, leadership as a board member of Foresight Diagnostics, and stock/options for CiberMed, Gritstone Bio, and Foresight Diagnostics. B.W.L. reports disclosures including grants with Varian Medical Systems, leadership as a board member of TibaRay, and stock holdings in TibaRay. L.K.V. reports disclosures including grants from RefleXion Medical., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Radiation-associated soft tissue sarcomas (RA-STS) are rare complications of patients receiving radiation therapy (RT) and are generally associated with a poor prognosis. Most of the literature surrounding RA-STS of the chest is centered on angiosarcoma. Therefore, we aim to document the management and outcome of patients with non-angiosarcoma RA-STS of the chest., Methods: We reviewed 17 patients (all female, median age 65 years) diagnosed with RA-STS. The most common primary malignancy was breast carcinoma (n = 15), with a median RT dose of 57.9 Gy. All patients underwent surgical resection; five patients (29%) received radiotherapy; and five patients (29%) received peri-operative chemotherapy., Results: The 5-year local recurrence and metastatic-free survival were 61% and 60%, while the 5-year disease-specific survival was 53%. Local recurrence was associated with death due to disease (HR 9.06, p = 0.01). Complications occurred in nine of patients, most commonly due to a wound complication (n = 7). At the most recent follow-up, the median Musculoskeletal Tumor Society Score was 63%., Conclusion: RA-STS involving the chest wall are aggressive tumors with a high risk of local relapse and death due to disease. Local recurrence was associated with death due to disease; as such, we recommend aggressive surgical management with evaluation for adjuvant therapies., (© 2024 Wiley Periodicals LLC.)

Background: The cardiac toxicity of radiotherapy (RT) can affect cancer survival rates over the long term. This has been confirmed in patients with breast cancer and lymphoma. However, there are few studies utilizing the two-dimensional speckle-tracking echocardiography (2D-STE) to evaluate the risk factors affecting radiation induced heart disease (RIHD), and there is a lack of quantitative data. Therefore, we intend to explore the risk factors for RIHD and quantify them using 2D-STE technology., Methods: We ultimately enrolled 40 patients who received RT for thoracic tumors. For each patient, 2D-STE was completed before, during, and after RT and in the follow up. We analyzed the sensitivity of 2D-STE in predicting RIHD and the relationship between RT parameters and cardiac systolic function decline., Results: Left ventricle global longitudinal strain (LVGLS), LVGLS of the endocardium (LVGLS-Endo), LVGLS of the epicardium (LVGLS-Epi), and right ventricle free-wall longitudinal strain (RVFWLS) decreased mid- and post-treatment compared with pre-treatment, whereas traditional parameters such as left ventricular ejection fraction (LVEF), cardiac Tei index (Tei), and peak systolic velocity of the free wall of the tricuspid annulus (s') did not show any changes. The decreases in the LVGLS and LVGLS-Endo values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with mean heart dose (MHD) (all P values < 0.05). The decreases in the LVGLS-Epi values between post- and pre-treatment and the ratios of the decreases to the baseline values were linearly correlated with the percentage of heart volume exposed to 5 Gy or more (V5) (P values < 0.05). The decrease in RVFWLS and the ratio of the decrease to the baseline value were linearly related to MHD and patient age (all P values < 0.05). Endpoint events occurred more frequently in the right side of the heart than in the left side. Patients over 56.5 years of age had a greater probability of developing right-heart endpoint events. The same was true for patients with MHD over 20.2 Gy in both the left and right sides of the heart., Conclusions: 2D-STE could detect damages to the heart earlier and more sensitively than conventional echocardiography. MHD is an important prognostic parameter for LV systolic function, and V5 may also be an important prognostic parameter. MHD and age are important prognostic parameters for right ventricle systolic function., (© 2024. The Author(s).)

Postoperative radiotherapy for breast cancer reportedly increases the risk of thoracic soft tissue sarcomas, particularly angiosarcomas; however, the risk in the Japanese population remains unknown. Therefore, this study aimed to investigate the incidence of thoracic soft tissue sarcoma among patients with breast cancer in Japan and determine its association with radiotherapy. This retrospective cohort study used data from the population-based cancer registry of the Osaka Prefecture. The inclusion criteria were female sex, age 20-84 years, diagnosis of breast cancer between 1990 and 2010, no supraclavicular lymph node or distant metastasis, underwent surgery and survived for at least 1 year. The primary outcome was the occurrence of thoracic soft tissue sarcomas 1 year or later after breast cancer diagnosis. Among the 13 762 patients who received radiotherapy, 15 developed thoracic soft tissue sarcomas (nine angiosarcomas and six other sarcomas), with a median time of 7.7 years (interquartile range, 4.0-8.6 years) after breast cancer diagnosis. Among the 27 658 patients who did not receive radiotherapy, four developed thoracic soft tissue sarcomas (three angiosarcomas and one other sarcoma), with a median time of 11.6 years after diagnosis. The 10-year cumulative incidence was higher in the radiotherapy cohort than in the non-radiotherapy cohort (0.087 vs. 0.0036%, P < 0.001). Poisson regression analysis revealed that radiotherapy increased the risk of thoracic soft tissue sarcoma (relative risk, 6.8; 95% confidence interval, 2.4-24.4). Thus, although rare, breast cancer radiotherapy is associated with an increased risk of thoracic soft tissue sarcoma in the Japanese population., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Objective: Radiation therapy (RT) may increase the risk of second cancer. This study aimed to determine the association between exposure to radiotherapy for the treatment of thoracic cancer (TC) and subsequent secondary lung cancer (SLC)., Materials and Methods: The Surveillance, Epidemiology, and End Results (SEER) database (from 1975 to 2015) was queried for TC. Univariate Cox regression analyses and multiple primary standardized incidence ratios (SIRs) were used to assess the risk of SLC. Subgroup analyses of patients stratified by latency time since TC diagnosis, age at TC diagnosis, and calendar year of TC diagnosis stage were also performed. Overall survival and SLC-related death were compared among the RT and no radiation therapy (NRT) groups by using Kaplan-Meier analysis and competitive risk analysis., Results: In a total of 329 129 observations, 147 847 of whom had been treated with RT. And 6799 patients developed SLC. Receiving radiotherapy was related to a higher risk of developing SLC for TC patients (adjusted HR, 1.25; 95% CI, 1.19-1.32; P < 0.001). The cumulative incidence of developing SLC in TC patients with RT (3.8%) was higher than the cumulative incidence (2.9%) in TC patients with NRT(P). The incidence risk of SLC in TC patients who received radiotherapy was significantly higher than the US general population (SIR, 1.19; 95% CI, 1.14-1.23; P < 0.050)., Conclusions: Radiotherapy for TC was associated with higher risks of developing SLC compared with patients unexposed to radiotherapy., (© 2024 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Background: Accurate and automated segmentation of thoracic organs-at-risk (OARs) is critical for radiotherapy treatment planning of thoracic cancers. However, this has remained a challenging task for four major reasons: (1) thoracic OARs have diverse morphologies; (2) thoracic OARs have low contrast with the background; (3) boundaries of thoracic OARs are blurry; (4) class imbalance issue caused by small organs., Purpose: To overcome the above challenges and achieve accurate and automated segmentation of thoracic OARs on thoracic CT., Methods: A novel cascaded framework based on mixed attention and multiscale information for thoracic OARs segmentation, called Cascaded-TOARNet. This cascaded framework comprises two stages: localization and segmentation. During the localization stage, TOARNet locates each organ to crop the regions of interest (ROIs). During the segmentation stage, TOARNet accurately segments the ROIs, and the segmentation results are merged into a complete result., Results: We evaluated our proposed method and other common segmentation methods on two public datasets: the AAPM Thoracic Auto-Segmentation Challenge dataset and the Segmentation of Thoracic Organs at Risk (SegTHOR) dataset. Our method demonstrated superior performance, achieving a mean Dice score of 92.6% on the SegTHOR dataset and 90.8% on the AAPM dataset., Conclusions: This segmentation method holds great promise as an essential tool for enhancing the efficiency of thoracic radiotherapy planning., (© 2023 American Association of Physicists in Medicine.)

Aim: To evaluate the treatment results, prognostic parameters, and treatment-related toxicity in patients with Ewing sarcoma (ES)/primitive neuroectodermal tumor (PNET) of the chest wall who underwent surgery, chemotherapy, and radiotherapy (RT) in a tertiary referral center., Methods: The data of 24 patients under 18 years of age with a histologic diagnosis of ES/PNET in the chest wall that received RT in our department between February 2003 and July 2020 were retrospectively evaluated. RT was applied to the primary site±whole involved chest wall and to the whole lung in patients with lung metastasis., Results: The median age was 8.5 years (range: 1.5 to 17 y), 15 (63%) patients were female and 9 were male (37%). The tumor localization was extrathoracic in 18 (75%) and intrathoracic in 6 (25%) patients. Mediastinal lymph node and distant metastasis (DM) was present in 5 (21%) and 4 (16%) cases at diagnosis, respectively. The median follow-up after RT was 47 months (range: 11 to 162 mo). The 2-year and 5-year overall survival, event-free survival, local recurrence-free survival, and pleural recurrence-free survival were 83% and 48%, 48% and 42%, 74% and 48%, and 61% and 52%, respectively. The overall local control rate was 83% and the pleural control rate was 67%. RT was well tolerated, with 1 case of grade 3 acute dermatitis and 1 case of grade 3 subacute radiation pneumonitis. Late toxicity was observed in 3 (13%) cases., Conclusion: Long-term survival can be achieved with extended-field RT even in patients with ES/PNET of the chest wall with DM. The low toxicity rates allow us to draw the conclusion that RT with modern techniques is an effective and safe treatment modality for these patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background/purpose: Central/ultra-central thoracic tumors are challenging to treat with stereotactic radiotherapy due potential high-grade toxicity. Stereotactic MR-guided adaptive radiation therapy (SMART) may improve the therapeutic window through motion control with breath-hold gating and real-time MR-imaging as well as the option for daily online adaptive replanning to account for changes in target and/or organ-at-risk (OAR) location., Materials/methods: 26 central (19 ultra-central) thoracic oligoprogressive/oligometastatic tumors treated with isotoxic (OAR constraints-driven) 5-fraction SMART (median 50 Gy, range 35-60) between 10/2019-10/2022 were reviewed. Central tumor was defined as tumor within or touching 2 cm around proximal tracheobronchial tree (PBT) or adjacent to mediastinal/pericardial pleura. Ultra-central was defined as tumor abutting the PBT, esophagus, or great vessel. Hard OAR constraints observed were ≤ 0.03 cc for PBT V40, great vessel V52.5, and esophagus V35. Local failure was defined as tumor progression/recurrence within the planning target volume., Results: Tumor abutted the PBT in 31 %, esophagus in 31 %, great vessel in 65 %, and heart in 42 % of cases. 96 % of fractions were treated with reoptimized plan, necessary to meet OAR constraints (80 %) and/or target coverage (20 %). Median follow-up was 19 months (27 months among surviving patients). Local control (LC) was 96 % at 1-year and 90 % at 2-years (total 2/26 local failure). 23 % had G2 acute toxicities (esophagitis, dysphagia, anorexia, nausea) and one (4 %) had G3 acute radiation dermatitis. There were no G4-5 acute toxicities. There was no symptomatic pneumonitis and no G2 + late toxicities., Conclusion: Isotoxic 5-fraction SMART resulted in high rates of LC and minimal toxicity. This approach may widen the therapeutic window for high-risk oligoprogressive/oligometastatic thoracic tumors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: The aim of this study was to analyze the setup error of the electronics portal image device (EPID) in intensity-modulated radiation therapy (IMRT) for thoracic tumors and the influence on the outward expansion distance of the target area., Patients and Methods: A total of 202 patients with chest tumors admitted to our hospital from March 2016 to March 2018 were selected as the observation subjects. All patients were treated with IMRT. The original plan was developed based on the SM90 obtained by the planning target volume (PTV) expansion method, and the new plan was obtained by shifting the isocenter coordinates of the treatment plan according to the positioning error value obtained by EPID. Before the treatment, EPID scans were performed. The electronic radiation field images (ERIs) were registered with the digitally reconstructed radiographic images (DRRs) generated by the treatment planning system using the image registration software, and the setup errors in the X, Y, and Z directions were further measured. The PTV was developed according to ERIs, and the setup error was simulated to obtain the PTV with 95% internal target volume (ITV) reaching the prescribed dose under the condition of a setup error. The outward expansion distance of clinical target volume (CTV) → PTV was calculated., Results: In this experiment, the setup errors in X, Y, and Z directions were (-2.00±1.16) mm, (0.16±1.14) mm, and (-0.55±1.16) mm, respectively. The systematic error in the Z direction was -3.00 mm, and the random error in the X direction was 3.30 mm. The CTV → PTV outward expansion distance was set as 7, 8 and 7 mm in the X direction, Y direction and Z direction, respectively. At this time, under the presence of setup error, the PTV D95 and the ITV V100 in the new plan were (62.23±3.85) Gy and (97.51±1.56) %, respectively, effectively ensuring that 95% ITV of 90% patients reached the prescribed dose. In contrast, the ITV D95 and ITV V100 in the presence of setup error were (56.11±5.26) Gy and (90.15±3.12) %, respectively, at a CTV → PTV outward expansion distance of 5 mm, which could not guarantee that 95% ITV of 90% patients reached the prescribed dose. In the presence of a setup error, the double-lung 5 Gy irradiation of the total heart volume (V5), the double-lung 20 Gy irradiation of the total heart volume (V20), mean lung dose (MLD), mean heart dose (MHD), and D1 cm3 of the new plan increased by 0.89%, 0.29%, 0.13%, 0.06%, and 5 Gy, respectively, compared with the original plan., Conclusions: In general, the first treatment of radiotherapy in thoracic tumors mostly has a certain degree of setup error, which is most evident in the X direction. When the CTV → PTV outward expansion distance is set at 7, 8, and 7 mm in the X direction, Y direction, and Z direction, respectively, it can effectively ensure that 95% ITV reach the prescribed dose in 90% of patients in the presence of a setup error. EPID helps to achieve the desired effect of radiotherapy, improves the efficacy of radiotherapy, and reduces the side effects caused by radiotherapy errors.

Radiation therapy in the thoracic region may deliver incidental ionizing radiation to the surrounding healthy structures, including the heart. Radio-induced heart toxicity has long been a concern in breast cancer and Hodgkin's lymphoma and was deemed a long-term event. However, recent data highlight the need to limit the dose to the heart in less favorable thoracic cancers too, such as lung and esophageal cancers in which incidental irradiation led to increased mortality. This article will summarize available cardiac dose constraints in various clinical settings and the types of radio-induced cardiovascular diseases encountered as well as delineation of cardiac subheadings and management of cardiac devices. Although still not completely deciphered, heart dose constraints remain intensively investigated and the mean dose to the heart is no longer the only dosimetric parameter to consider since the left anterior descending artery as well as the left ventricle should also be part of dosimetry constraints., (Copyright © 2023. Published by Elsevier Masson SAS.)

Thoracic tumors include more than one hundred histopathological subtypes. Rare thoracic malignancies can be defined as representing less than 1% of all thoracic tumors. The European Rare Cancer Surveillance Project (RARECARE) identified rarity as an incidence less than 6 for 100,000 people, with significant difference of prevalence between them. Modalities of treatment for these pathologies include surgery, radiotherapy, and systemic therapies. In this article, we aim to discuss role and techniques of radiotherapy in management of rare solid thoracic tumors in adults, focusing on different anatomical locations such as lung parenchyma, mediastinum, vessels, chest wall and pleural cavity., (Copyright © 2023 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Objective: Radiation therapy is an important method for the treatment of chest tumors. This study discussed the placement error of three-dimensional (3D) conformal intensity-modulated radiotherapy in patients with different types of chest tumors and analyzed the relevant influencing factors., Patients and Methods: 100 patients with chest tumors diagnosed and treated in our hospital from March 2016 to March 2018 were randomly selected as research subjects, including 42 cases of esophageal cancer, 44 cases of breast cancer, and 14 cases of lung cancer. All patients underwent 3D conformal radiotherapy. The setup errors of patients with esophageal cancer, breast cancer, and lung cancer were detected after 3D conformal radiotherapy. Besides, the influencing factors of 3D conformal for thoracic tumors were analyzed by multiple linear regression analysis., Results: After 3D conformal radiotherapy, the systematic errors of patients with esophageal cancer in X-axis, Y-axis, and Z-axis were -0.10, 1.26 and 0.07, respectively, while the random errors in X-axis, Y-axis, and Z-axis were 1.18, -1.14, and 0.97 respectively. The times for the absolute values of the positioning error with a range of ≤5 mm in X-axis, Y-axis, and Z-axis were 40 (95.24%), 2 (4.76%) and 36 (85.71%), while these with a range of >5 mm in X-axis, Y-axis, and Z-axis were 6 (14.29%), 41 (97.62%) and 1 (2.38%), respectively. For patients with breast cancer, the systematic errors and random errors in X-axis, Y-axis, and Z-axis are -0.19, 1.19, and 0.15, as well as 0.97, 0.02 and 1.29, respectively. The times for the absolute values of the positioning error with a range of ≤5 mm and >5 mm were 41 (93.18%), 3 (6.82%), and 36 (81.82%), as well as 8 (18.18%), 42 (95.45%) and 2 (4.55%), severally. For patients with lung cancer, the systematic errors and random errors in X-axis, Y-axis, and Z-axis were 0.14, 1.42, and 0.15, as well as 1.35, -0.23 and 1.12, respectively. The times for the absolute values of the positioning error with the range of ≤5 mm and >5 mm were 14 (93.33%), 1 (6.67%), and 11 (73.33%), as well as 4 (26.67%), 14 (93.33%) and 1 (6.67%) after 3D conformal radiotherapy. After multiple linear regression analyses, gender and lung volume were the influencing factors of Z-axis setup error, and the lesion location was the influence factor of Y-axis setup error (p<0.05)., Conclusions: There are certain positioning errors in the X-axis, Y-axis, and Z-axis directions of thoracic tumors receiving 3D conformal radiotherapy. Gender, lung volume, and lesion location are all important factors that affect the placement error. The results of this study provide a certain reference for the positioning error of radiation therapy for thoracic tumors, which is conducive to improving the accuracy of radiotherapy and better protecting the surrounding tissues.

Purpose: Despite the anticipated clinical benefits of intensity-modulated proton therapy (IMPT), plan robustness may be compromised due to its sensitivity to patient treatment uncertainties, especially for tumours with large motion. In this study, we investigated treatment course-wise plan robustness for intra-thoracic tumours with large motion comparing a 4D pre-clinical evaluation method (4DREM) to our clinical 3D/4D dose reconstruction and accumulation methods., Materials and Methods: Twenty patients with large target motion (>10 mm) were treated with five times layered rescanned IMPT. The 3D-robust optimised plans were generated on the averaged planning 4DCT. Using multiple 4DCTs, treatment plan robustness was assessed on a weekly and treatment course-wise basis through the 3D robustness evaluation method (3DREM, based on averaged 4DCTs), the 4D robustness evaluation method (4DREM, including the time structure of treatment delivery and 4DCT phases) and 4D dose reconstruction and accumulation (4DREAL, based on fraction-wise information)., Results: Baseline target motion for all patients ranged from 11-17 mm. For the offline adapted course-wise dose assessment, adequate target dose coverage was found for all patients. The target volume receiving 95% of the prescription dose was consistent between methods with 16/20 patients showing differences < 1%. 4DREAL showed the highest target coverage (99.8 ± 0.6%, p < 0.001), while no differences were observed between 3DREM and 4DREM (99.3 ± 1.3% and 99.4 ± 1.1%, respectively)., Conclusion: Our results show that intra-thoracic tumours can be adequately treated with IMPT in free breathing for target motion amplitudes up to 17 mm employing any of the accumulation methods. Anatomical changes, setup and range errors demonstrated a more severe impact on target coverage than motion in these patients treated with fractionated proton radiotherapy., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

The lung volume receiving low-dose irradiation has been reported to increase in volumetric-modulated arc radiotherapy (VMAT) compared with three-dimensional conformal radiotherapy (3DCRT) for thoracic esophageal cancer, which raises concerns regarding radiation pneumonitis (RP) risk. This single institutional retrospective cohort study aimed to explore whether VMAT for thoracic esophageal cancer was associated with RP. Our study included 161 patients with thoracic esophageal cancer, of whom 142 were definitively treated with 3DCRT and 39 were treated with VMAT between 2008 and 2018. Radiotherapy details, dose-volume metrics, reported RP risk factors and RP incidence were collected. The RP risk factors were assessed via multivariate analysis. Dose-volume analysis showed that VMAT delivered more conformal dose distributions to the target volume (P < 0.001) and reduced V30 Gy of heart (57% vs 41%, P < 0.001) but increased V5 Gy (54% vs 41%, P < 0.001) and V20 Gy (20% vs 17%, P = 0.01) of lungs compared with 3DCRT. However, the 1-year incidence rates of RP did not differ between the two techniques (11.3% in 3DCRT vs 7.7% in VMAT, P = 0.53). The multivariate analysis suggested that the presence of interstitial lung disease (ILD) (P = 0.01) and V20 Gy of lungs ≥20% (P = 0.008) were associated with RP. Conclusively, VMAT increased the lung volume receiving low to middle doses irradiation, although this might not be associated with RP. Further studies are needed to investigate the effect of using VMAT for delivering conformal dose distributions on RP., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Radiotherapy remains an important treatment modality for patients with chest malignancies; this is particularly true in patients with breast cancer and Hodgkin lymphoma as well as lung, esophageal, and other mediastinal tumors. More than half of patients with these conditions receive radiotherapy at some point. With the development of new treatment modalities, we are witnessing an improvement of overall survival requiring carefully watching of acute and chronic toxicity of radiation therapy. The challenge is not to ignore radiotherapy's side effects in order to explore and prevent them in the future. Strategies for optimizing thoracic radiotherapy and the advent of innovative techniques may represent an encouraging way to decrease thoracic toxicities. We reviewed the literature to identify these cases of toxicity, which are sometimes forgotten, and others, which have recently been described but remain poorly known., (Copyright © 2022 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Purpose: Owing to adjacent critical organs, the aggressive multimodality local therapy necessary for Ewing sarcoma of the chest wall is a challenge. Our previous review of historical outcomes at our institution revealed suboptimal disease control and a high incidence of grade ≥3 toxic effects in patients treated before 2006. The purpose of this study was to evaluate changes during the past decade since the introduction of proton therapy., Methods and Materials: Thirty-nine consecutive pediatric patients with a chest wall Ewing sarcoma treated between 2006 and 2020 at the University of Florida were identified. The median maximum tumor diameter was 10 cm (range, 4-28 cm). At diagnosis, 19 patients had local disease and the others had a pleural effusion (11), pleural nodules (5), or pulmonary metastases (4). Patients were treated with chemotherapy regimens according to contemporary North American and European protocols: 7 were treated with preoperative, 18 with postoperative, and 14 with definitive radiation. Preceding primary site treatment, 15 patients required hemithorax radiation and 4 patients underwent whole-lung irradiation using photon techniques. The total median radiation dose to the primary tumor was 52.8 GyRBE [relative biological effectiveness] (range, 44.4-55.8 GyRBE)., Results: With a median follow-up of 4 years (range, 0.7-14.7 years), the 5-year local control, progression-free survival, and overall survival rates were 97.2%, 74.4%, and 81.6%, respectively, for the whole cohort. For the 19 patients with nonmetastatic disease, the 5-year local control, progression-free survival, and overall survival rates were 100%, 78.9%, and 78.9%, respectively. No patients developed grade ≥4 toxic effects. Two patients (5%) experienced grade 3 toxic effects related to multimodality treatment; both were patients who required surgery to correct scoliosis. Two patients (5%) developed grade 2 pneumonitis., Conclusions: Compared with our prior published institutional experience, our data suggest improvements in disease control and multimodality toxic effects since the introduction of proton therapy. This should be confirmed with a larger sample size and longer follow-up., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We present the update of the recommendations of the French society of oncological radiotherapy on respiratory motion management for external radiotherapy treatment. Since twenty years and the report 62 of ICRU, motion management during the course of radiotherapy treatment has become an increasingly significant concern, particularly with the development of hypofractionated treatments under stereotactic conditions, using reduced safety margins. This article related orders of motion amplitudes for different organs as well as the definition of the margins in radiotherapy. An updated review of the various movement management strategies is presented as well as main technological solutions enabling them to be implemented: when acquiring anatomical data, during planning and when carrying out treatment. Finally, the management of these moving targets, such as it can be carried out in radiotherapy departments, will be detailed for a few concrete examples of localizations (abdominal, thoracic and hepatic)., (Copyright © 2021 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Objective: Single prolonged breath-holds of >5 min can be obtained in cancer patients. Currently, however, the preparation time in each radiotherapy session is a practical limitation for clinical adoption of this new technique. Here, we show by how much our original preparation time can be shortened without unduly compromising breath-hold duration., Methods: 44 healthy subjects performed single prolonged breath-holds from 60% O 2 and mechanically induced hypocapnia. We tested the effect on breath-hold duration of shortening preparation time (the durations of acclimatization, hyperventilation and hypocapnia) by changing these durations and or ventilator settings., Results: Mean original breath-hold duration was 6.5 ± 0.2 (standard error) min. The total original preparation time (from connecting the facemask to the start of the breath-hold) was 26 ± 1 min. After shortening the hypocapnia duration from 16 to 5 min, mean breath-hold duration was still 6.1 ± 0.2 min ( ns vs the original). After abolishing the acclimatization and shortening the hypocapnia to 1 min (a total preparation time now of 9 ± 1 min), a mean breath-hold duration of >5 min was still possible (now significantly shortened to 5.2 ± 0.6 min, p < 0.001). After shorter and more vigorous hyperventilation (lasting 2.7 ± 0.3 min) and shorter hypocapnia (lasting 43 ± 4 s), a mean breath-hold duration of >5 min (5.3 ± 0.2 min, p < 0.05) was still possible. Here, the final total preparation time was 3.5 ± 0.3 min., Conclusions: These improvements may facilitate adoption of the single prolonged breath-hold for a range of thoracic and abdominal radiotherapies especially involving hypofractionation., Advances in Knowledge: Multiple short breath-holds improve radiotherapy for thoracic and abdominal cancers. Further improvement may occur by adopting the single prolonged breath-hold of >5 min. One limitation to clinical adoption is its long preparation time. We show here how to reduce the mean preparation time from 26 to 3.5 min without compromising breath-hold duration.

Background: We sought to test the hypothesis that thoracic radiation therapy (RT) is associated with impaired myocardial flow reserve (MFR), a measure of coronary vasomotor dysfunction., Methods: We retrospectively studied thirty-five consecutive patients (71% female, mean ± standard deviation (SD) age: 66 ± 11 years) referred clinically for positron emission tomography/computed tomography (PET/CT) myocardial perfusion imaging at a median (interquartile range, IQR) interval of 4.3 (2.1, 9.7) years following RT for a variety of malignancies. Radiation dose-volume histograms were generated for the heart and coronary arteries for each patient., Results: The median (IQR) of mean cardiac radiation doses was 12.0 (1.2, 24.2) Gray. There were significant inverse correlations between mean radiation dose and global MFR (MFR Global ) and MFR in the left anterior descending artery territory (MFR LAD ): Pearson's correlation coefficient = - .37 (P = .03) and - .38 (P = .03), respectively. For every one Gray increase in mean cardiac radiation dose, there was a mean ± standard error decrease of .02 ± .01 in MFR Global (P = .04) and MFR LAD (P = .03) after adjustment., Conclusions: In patients with a history of RT clinically referred for cardiac stress PET, we found an inverse correlation between mean cardiac radiation dose and coronary vasomotor function., (© 2020. American Society of Nuclear Cardiology.)

Purpose: The accuracy of target delineation for node-positive thoracic tumors is dependent on both four-dimensional computed tomography (4D-CT) and contrast-enhanced three-dimensional (3D)-CT images; these scans enable the motion visualization of tumors and delineate the nodal areas. Combining the two techniques would be more effective; however, currently, there is no standard protocol for the contrast media injection parameters for contrast-enhanced 4D-CT (CE-4D-CT) scans because of its long scan durations and complexity. Thus, we aimed to perform quantitative and qualitative assessments of the image quality of single contrast-enhanced 4D-CT scans to simplify this process and improve the accuracy of target delineation in order to replace the standard clinical modality involved in administering radiotherapy for thoracic tumors., Methods: Ninety consecutive patients with thoracic tumors were randomly and parallelly assigned to one of nine subgroups subjected to CE-4D-CT scans with the administration of contrast agent volume equal to the patient's weight but different flow rate and scan delay time (protocol A1: flow rate of 2.0 ml/s, delay time of 15 s; A2: 2.0 ml/s, 20 s; A3: 2.0 ml/s, 25 s; B1: 2.5 ml/s, 15 s; B2: 2.5 ml/s, 20 s; B3: 2.5 ml/s, 25 s; C1: 3.0 ml/s, 15 s; C2: 3.0 ml/s, 20 s; C3: 3.0 ml/s, 25 s). The Hounsfield unit (HU) values of the thoracic aorta, pulmonary artery stem, pulmonary veins, carotid artery, and jugular vein were acquired for each protocol. Both quantitative and qualitative image analysis and delineation acceptability were assessed., Results: The results revealed significant differences among the nine protocols. Enhancement of the vascular structures in mediastinal and perihilar regions was more effective with protocol A1 or A2; however, when interested in the region of superior mediastinum and supraclavicular fossa, protocol C2 or C3 is recommended., Conclusion: Qualitatively acceptable enhancement on contrast-enhanced 4D-CT images of thoracic tumors can be obtained by varying the flow rate and delay time when minimal contrast agent is used., (© 2021. The Author(s).)

Radiation-induced cardiopulmonary injuries are the most common and intractable side effects that are entwined with radiotherapy for thorax cancers. However, the therapeutic options for such complications have yielded disappointing results in clinical applications. Here, we reported that gut microbiota-derived l-Histidine and its secondary metabolite imidazole propionate (ImP) fought against radiation-induced cardiopulmonary injury in an entiric flora-dependent manner in mouse models. Local chest irradiation decreased the level of l-Histidine in fecal pellets, which was increased following fecal microbiota transplantation. l-Histidine replenishment via an oral route retarded the pathological process of lung and heart tissues and improved lung respiratory and heart systolic function following radiation exposure. l-Histidine preserved the gut bacterial taxonomic proportions shifted by total chest irradiation but failed to perform radioprotection in gut microbiota-deleted mice. ImP, the downstream metabolite of l-Histidine, accumulated in peripheral blood and lung tissues following l-Histidine replenishment and protected against radiation-induced lung and heart toxicity. Orally gavaged ImP could not enter into the circulatory system in mice through an antibiotic cocktail treatment. Importantly, ImP inhibited pyroptosis to nudge lung cell proliferation after radiation challenge. Together, our findings pave a novel method of protection against cardiopulmonary complications intertwined with radiotherapy in pre-clinical settings and underpin the idea that gut microbiota-produced l-Histidine and ImP are promising radioprotective agents.

Hybrid magnetic resonance (MR)-guided linear accelerators represent a new horizon in the field of radiation oncology. By harnessing the favorable combination of on-board MR-imaging with the possibility to daily recalculate the treatment plan based on real-time anatomy, the accuracy in target and organs-at-risk identification is expected to be improved, with the aim to provide the best tailored treatment. To date, two main MR-linac hybrid machines are available, Elekta Unity and Viewray MRIdian. Of note, compared to conventional linacs, these devices raise practical issues due to the positioning phase for the need to include the coil in the immobilization procedure and in order to perform the best reproducible positioning, also in light of the potentially longer treatment time. Given the relative novelty of this technology, there are few literature data regarding the procedures and the workflows for patient positioning and immobilization for MR-guided daily adaptive radiotherapy. In the present narrative review, we resume the currently available literature and provide an overview of the positioning and setup procedures for all the anatomical districts for hybrid MR-linac systems., (© 2021. The Author(s).)

This article analyzes the accuracy of needle track and dose of a 3-dimensional printing template (3DPT) in the treatment of thoracic tumor with radioactive I-125 seed implantation (RISI). A total of 28 patients were included. The technical process included: (i) preoperative CT positioning, (ii) preoperative planning design, (iii) 3DPT design and printing, (iv) 3DPT alignment, (v) puncture and seed implantation. The errors of needle position and dosimetric parameters were analyzed. A total of 318 needles were used. The mean errors in needle depth, needle insertion point, needle tip and needle angle were 0.52 ± 0.48 cm, 3.4 ± 1.7 mm, 4.4 ± 2.9 mm and 2.8 ± 1.7°, respectively. The differences between actual needle insertion angle and needle depth and those designed in the preoperative were statistically significant (p < 0.05). The mean values of all the errors of the chest wall cases were smaller than those of the lungs, and the differences were statistically significant (p < 0.05). There was no significant difference between the D90 calculated in the postoperative plan and those designed in the preoperative and intraoperative plans (p > 0.05). Some dosimetric parameters of preoperative plans such as V100, V200, CI and HI were not consistent with that of preoperative plans, and the difference was statistically significant (p < 0.05). However, there were no statistical difference in the dosimetric parameters between the postoperative plans and intraoperative plans (p > 0.05). We conclude that for thoracic tumors, even under the guidance of 3DPT, there will be errors. The plan should be optimized in real time during the operation., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

Purpose Acute radiation-induced esophagitis (ARIE) leads to treatment delays, decreased quality of life (QOL), and secondary adverse events such as weight loss. Grade 3 ARIE occurs in 15%-30% of patients undergoing radiotherapy to the esophagus, leading to disruption or discontinuation of treatment. The purpose of this study was to assess the effects of glutamine, a common nutritional supplement, on ARIE in patients with thoracic malignancies. Patients and methods This double-blind, placebo-controlled trial enrolled patients with advanced thoracic malignancies receiving concurrent chemotherapy/radiotherapy or radiotherapy alone, with radiation doses to the esophagus ≥45 Gy. Patients were randomized (1:1) to receive 4 g of glutamine or glycine placebo twice daily. The primary objective was to determine whether glutamine decreases the severity of ARIE in these patients. Secondary objectives included assessment of the effects of glutamine on other measures of ARIE, weight, symptom burden measure assessed by the MD Anderson Symptom Inventory (MDASI-HN) questionnaire and the toxicity profile of glutamine. Results At the time of interim analysis, 53 patients were enrolled: 27 in the glutamine arm and 26 in the placebo arm. There was no difference in the incidence of esophagitis in the first 6 weeks of radiotherapy between the glutamine and placebo arms (74% versus 68%; P = 1.00). There were no significant differences between the two arms for time to onset of esophagitis. The duration of ARIE was shorter (6.3 versus 7.1 weeks; P = 0.54) and median weight loss was lower (0.9 kg versus 2.8 kg; p = 0.83) in the glutamine arm versus the placebo arm. The groups differ significantly in core symptom severity (2.1 vs 1.5, p < .03) but not in head and neck specific symptom severity (1.2 vs 1.1, p < .60) nor in symptom interference (2.1 vs 1.7, p < .22). There was no grade 3 or higher adverse event at least possibly related to glutamine. The study was terminated for futility following interim analysis. Conclusion Oral glutamine was not associated with significant improvement in severity of ARIE, weight loss, head and neck specific symptoms or symptom interference compared with placebo in patients with advanced thoracic malignancies receiving radiotherapy to the esophagus.Clinical trial information. NCT01952847, and date of registration is September 30, 2013., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Introduction: Regardless of its rarity, and indolent clinical course, chest wall tumor places high morbidity and burden on patients especially when invasion to a neighboring structure is found. Once detected, surgery is the cornerstone for treatment of such etiology combined with chemo-radiotherapy. In order to maintain intact respiratory function, chest wall reconstruction must be performed whenever resection is done. Herein, we present a case of chest wall tumor that necessitated three ribs and part of hemidiaphragm resection and reconstruction with optimal post-operative results., Case Presentation: A 27-year-old male patient who had chest wall and diaphragm reconstruction for a chest wall Ewing sarcoma, using a single patch of expanded polytetrafluoroethylene (ePTFE) mesh with diaphragm implanted into the middle of the mesh. There were no immediate nor post-operative complications. The patient received post-operative radiotherapy with good functional and cosmetic results., Conclusion: We present a novel and safe technique for combined chest wall and diaphragmatic resection following excision of an invading tumor while ensuring cosmesis and functionality of the ribcage as well as the diaphragm., (© 2021. The Author(s).)

Purpose: Respiratory motion of thoracic organs poses a severe challenge for the administration of image-guided radiotherapy treatments. Providing online and up-to-date volumetric information during free breathing can improve target tracking, ultimately increasing treatment efficiency and reducing toxicity to surrounding healthy tissue. In this work, a novel population-based generative network is proposed to address the problem of 3D target location prediction from 2D image-based surrogates during radiotherapy, thus enabling out-of-plane tracking of treatment targets using images acquired in real time., Methods: The proposed model is trained to simultaneously create a low-dimensional manifold representation of 3D non-rigid deformations and to predict, ahead of time, the motion of the treatment target. The predictive capabilities of the model allow correcting target location errors that can arise due to system latency, using only a baseline volume of the patient anatomy. Importantly, the method does not require supervised information such as ground-truth registration fields, organ segmentation, or anatomical landmarks., Results: The proposed architecture was evaluated on both free-breathing 4D MRI and ultrasound datasets. Potential challenges present in a realistic therapy, like different acquisition protocols, were taken into account by using an independent hold-out test set. Our approach enables 3D target tracking from single-view slices with a mean landmark error of 1.8 mm, 2.4 mm and 5.2 mm in volunteer MRI, patient MRI and US datasets, respectively, without requiring any prior subject-specific 4D acquisition., Conclusions: This model presents several advantages over state-of-the-art approaches. Namely, it benefits from an explainable latent space with explicit respiratory phase discrimination. Thanks to the strong generalization capabilities of neural networks, it does not require establishing inter-subject correspondences. Once trained, it can be quickly deployed with an inference time of only 8 ms. The results show the capability of the network to predict future anatomical changes and track tumors in real time, yielding statistically significant improvements over related methods.

Purpose: To investigate the interobserver variability (IOV) in target volume delineation of definitive radiotherapy for thoracic esophageal cancer (TEC) among cancer centers in China, and ultimately improve contouring consistency as much as possible to lay the foundation for multi-center prospective studies., Methods: Sixteen cancer centers throughout China participated in this study. In Phase 1, three suitable cases with upper, middle, and lower TEC were chosen, and participants were asked to contour a group of gross tumor volume (GTV-T), nodal gross tumor volume (GTV-N) and clinical target volume (CTV) for each case based on their routine experience. In Phase 2, the same clinicians were instructed to follow a contouring protocol to re-contour another group of target volume. The variation of the target volume was analyzed and quantified using dice similarity coefficient (DSC)., Results: Sixteen clinicians provided routine volumes, whereas ten provided both routine and protocol volumes for each case. The IOV of routine GTV-N was the most striking in all cases, with the smallest DSC of 0.37 (95% CI 0.32-0.42), followed by CTV, whereas GTV-T showed high consistency. After following the protocol, the smallest DSC of GTV-N was improved to 0.64 (95% CI 0.45-0.83, P = 0.005) but the DSC of GTV-T and CTV remained constant in most cases., Conclusion: Variability in target volume delineation was observed, but it could be significantly reduced and controlled using mandatory interventions.

Background: Radiation-induced pneumonitis (RP) is a non-negligible and sometimes life-threatening complication among patients with thoracic radiation. We initially aimed to ascertain the predictive value of acute radiation-induced esophagitis (SARE, grade ≥ 2) to symptomatic RP (SRP, grade ≥ 2) among thoracic cancer patients receiving radiotherapy. Based on that, we established a novel nomogram model to provide individualized risk assessment for SRP., Methods: Thoracic cancer patients who were treated with thoracic radiation from Jan 2018 to Jan 2019 in Shandong Cancer Hospital and Institute were enrolled prospectively. All patients were followed up during and after radiotherapy (RT) to observe the development of esophagitis as well as pneumonitis. Variables were analyzed by univariate and multivariate analysis using the logistic regression model, and a nomogram model was established to predict SRP by "R" version 3.6.0., Results: A total of 123 patients were enrolled (64 esophageal cancer, 57 lung cancer and 2 mediastinal cancer) in this study prospectively. RP grades of 0, 1, 2, 3, 4 and 5 occurred in 29, 57, 31, 0, 3 and 3 patients, respectively. SRP appeared in 37 patients (30.1%). In univariate analysis, SARE was shown to be a significant predictive factor for SRP (P < 0.001), with the sensitivity 91.9% and the negative predictive value 93.5%. The incidence of SRP in different grades of ARE were as follows: Grade 0-1: 6.5%; Grade 2: 36.9%; Grade 3: 80.0%; Grade 4: 100%. Besides that, the dosimetric factors considering total lung mean dose, total lung V5, V20, ipsilateral lung mean dose, ipsilateral lung V5, and mean esophagus dose were correlated with SRP (all P < 0.05) by univariate analysis. The incidence of SRP was significantly higher in patients whose symptoms of RP appeared early. SARE, mean esophagus dose and ipsilateral mean lung dose were still significant in multivariate analysis, and they were included to build a predictive nomogram model for SRP., Conclusions: As an early index that can reflect the tissue's radiosensitivity visually, SARE can be used as a predictor for SRP in patients receiving thoracic radiation. And the nomogram containing SARE may be fully applied in future's clinical work.

Radiation therapy (RT) plays an important role in the curative treatment of a variety of thoracic malignancies. However, delivery of tumoricidal doses with conventional photon-based RT to thoracic tumors often presents unique challenges. Extraneous dose deposited along the entrance and exit paths of the photon beam increases the likelihood of significant acute and delayed toxicities in cardiac, pulmonary, and gastrointestinal structures. Furthermore, safe dose-escalation, delivery of concomitant systemic therapy, or reirradiation of a recurrent disease are frequently not feasible with photon RT. In contrast, protons have distinct physical properties that allow them to deposit a high irradiation dose in the target, while leaving a negligible exit dose in the adjacent organs at risk. Proton beam therapy (PBT), therefore, can reduce toxicities with similar antitumor effect or allow for dose escalation and enhanced antitumor effect with the same or even lower risk of adverse events, thus potentially improving the therapeutic ratio of the treatment. For thoracic malignancies, this favorable dose distribution can translate to decreases in treatment-related morbidities, provide more durable disease control, and potentially prolong survival. This review examines the evolving role of PBT in the treatment of thoracic malignancies and evaluates the data supporting its use., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction : Radiotherapy is an integral component in the treatment of the majority of thoracic malignancies. By taking advantage of the steep dose fall-off characteristic of protons combined with modern optimization and delivery techniques, proton beam therapy (PBT) has emerged as a potential tool to improve oncologic outcomes while reducing toxicities from treatment. Areas covered : We review the physical properties and treatment techniques that form the basis of PBT as applicable for thoracic malignancies, including a brief discussion on the recent advances that show promise to enhance treatment planning and delivery. The dosimetric advantages and clinical outcomes of PBT are critically reviewed for each of the major thoracic malignancies, including lung cancer, esophageal cancer, mesothelioma, thymic cancer, and primary mediastinal lymphoma. Expert opinion : Despite clear dosimetric benefits with PBT in thoracic radiotherapy, the improvement in clinical outcomes remains to be seen. Nevertheless, with the incorporation of newer techniques, PBT remains a promising modality and ongoing randomized studies will clarify its role to determine which patients with thoracic malignancies receive the most benefit. Re-irradiation, advanced disease requiring high cardio-pulmonary irradiation volume and younger patients will likely derive maximum benefit with modern PBT.

Background: In interstitial brachytherapy, needles must be inserted in a regular, parallel arrangement to ensure a uniform target dose distribution and conformal distribution to the target. It is generally difficult to achieve this in thoracic tumors because of obstruction by the ribs. Furthermore, insertion of multiple needles may cause the patient considerable harm and could expose him/her to additional risks. Thus, we propose the single-dwell-position method, discuss its applicability, and compare it with the actual multiple-needle method using dosimetry. The aim of this study was to evaluate the necessity for multiple needles with irregular alignment in interstitial brachytherapy for thoracic tumors., Methods: Twelve patients' interstitial brachytherapy plans were reviewed. The single-dwell-position interstitial brachytherapy plans, wherein one needle was hypothetically inserted, were compared with the actual multiple-needle plans. Dose parameters, including clinical target volume (CTV) and volumes of the lung, spinal cord, heart, and ribs, were compared. We also evaluated the correlation between CTV size and dose difference in the lungs. The nonparametric Wilcoxon test was used., Results: There were no statistically significant differences in the doses achieved with the single-dwell-position plans and actual multiple-needle plans. The correlation between the CTV size and dose difference in the lungs was weak., Conclusions: Irregularly arranged multiple-needle interstitial brachytherapy does not provide superior doses to the lung, heart, spinal cord, or ribs compared with single-dwell-position plans. If regular arrangement of multiple needles is difficult to achieve, the multiple-needle scheme is not the only viable option., Competing Interests: None

User-guided deformable image registration (DIR) has allowed users to actively participate in the DIR process and is expected to improve DIR accuracy. The purpose of this study was to evaluate the time required for and effect of user-guided DIR on registration accuracy for thoracic images among users. In this study, 4-dimensional computed tomographic images of 10 thoracic cancer patients were used. The dataset for these patients was provided by DIR-Lab (www.dir-lab.com) and included a coordinate list of anatomical landmarks (300 bronchial bifurcations). Four medical physicists from different institutions performed DIR between peak-inhale and peak-exhale images with/without the user-guided DIR tool, Reg Refine, implemented in MIM Maestro (MIM software, Cleveland, OH). DIR accuracy was quantified by using target registration errors (TREs) for 300 anatomical landmarks in each patient. The average TREs with user-guided DIR in the 10 images by the 4 medical physicists were 1.48, 1.80, 3.46, and 3.55 mm, respectively, whereas the TREs without user-guided DIR were 3.28, 3.45, 3.56, and 3.28 mm, respectively. The average times taken by the 4 physicists to use the user-guided DIR were 10.0, 6.7, 7.1, and 8.0 min, respectively. This study demonstrated that user-guided DIR can improve DIR accuracy and requires only a moderate amount of time (<10 min). However, 2 of the 4 users did not show much improvement in DIR accuracy, which indicated the necessity of training prior to use of user-guided DIR., (Copyright © 2019 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Purpose: Clinical trials are considered the gold standard in evidence-based medicine, yet few patients with cancer ultimately enroll. Here we examine patients screened for thoracic radiation oncology clinical trials to better understand enrollment trends., Methods and Materials: A prospective database tracking screening and enrollment for patients referred for thoracic radiation oncology consultation at our institution from 2016 to 2019 was evaluated. Proportional enrollment rates, patient and disease characteristics, self-reported socioeconomic factors, and reasons for ineligibility or nonenrollment across 17 radiation therapy trials were compared., Results: Enrollment data on 2372 patients were available for analysis. Of these patients, 40.0% (949) were deemed "not eligible" (NE) for any trial or were unwilling to be further screened. Reasons for ineligibility included stage (44%), histology (13%), radiation therapy not indicated (12%), patient decision (7%), and enrollment in a competing medical or surgical oncology trial (5%). The remaining 60.0% (1423) were "potentially eligible" (PE) for one or more trials. Most had non-small cell lung cancer (71%) or esophageal cancer (16%), and there were significantly fewer stage IV PE (29%) versus NE (49%) patients (P < .0001). Of 2372 patients, 281 (11.9%) enrolled. Notable reasons for nonenrollment were inclusion and exclusion criteria (58%), patients declining enrollment (14%), and physician decision (5%). The proportion of white patients was higher in the PE versus NE group (82.5% vs 75.8%; P < .001). Additionally, white race (87.9% vs 81.2%; P = .008), English language preference (96.4% vs 92.9%; P = .032), and non-Hispanic/Latino ethnicity (94.0% vs 90.1%; P = .042) were significantly different in enrolled versus nonenrolled PE patients., Conclusions: Only 12% of patients screened for radiation therapy trials ultimately enrolled, and more than two-thirds had no trial available or were found ineligible. In addition, 19% of potential eligible patients did not enroll because the patient or physician declined. Future trials may benefit from pragmatic designs with more inclusive enrollment criteria and multidisciplinary engagement of referring providers., (Copyright © 2020. Published by Elsevier Inc.)

Objectives: We aimed to evaluate the impact of collaborative discussion between diagnostic radiologists and radiation oncologists on radiation oncology management for thoracic oncology patients., Methods: We reviewed cases presented at multidisciplinary thoracic tumor boards (TTB) (n = 122) and diagnostic radiology/radiation oncology rounds (DR/ROR) (n = 45). Changes in planned radiation management following imaging discussion were categorized-no change, timing change, and treatment volume change. Phase of care was also classified. In DR/ROR, radiation oncologists were surveyed regarding (1) change in radiation oncology management and (2) change in confidence (both 5-point Likert scales)., Results: Discussion of imaging with a radiologist changed radiation oncology management in 31.1% of TTB cases and 68.9% of DR/ROR cases (P < 0.001). Changes to the timing of initiating radiation therapy occurred with similar frequency in the 2 settings (31.1% vs 46.7%, P = 0.063). Changes to target volume occurred more frequently in DR/ROR (35.6% vs <1%), P < 0.001. Over half of imaging discussions in DR/ROR resulted in at least "moderate" change in radiation oncology management, and the level of confidence held by the radiation oncologists increased following discussion with radiologists in 95.6% of cases., Conclusion: Collaborative discussions between radiation oncologists and diagnostic radiologists in a multispecialty tumor board and in targeted 2-specialty rounds are not redundant, but result in different management changes and at different phases of care. Our study emphasizes the importance of consultation with physicians as an area where radiologists can add value, specifically the added benefit of smaller collaborative discussions., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Automatic segmentation offers many benefits for radiotherapy treatment planning; however, the lack of publicly available benchmark datasets limits the clinical use of automatic segmentation. In this work, we present a well-curated computed tomography (CT) dataset of high-quality manually drawn contours from patients with thoracic cancer that can be used to evaluate the accuracy of thoracic normal tissue auto-segmentation systems., Acquisition and Validation Methods: Computed tomography scans of 60 patients undergoing treatment simulation for thoracic radiotherapy were acquired from three institutions: MD Anderson Cancer Center, Memorial Sloan Kettering Cancer Center, and the MAASTRO clinic. Each institution provided CT scans from 20 patients, including mean intensity projection four-dimensional CT (4D CT), exhale phase (4D CT), or free-breathing CT scans depending on their clinical practice. All CT scans covered the entire thoracic region with a 50-cm field of view and slice spacing of 1, 2.5, or 3 mm. Manual contours of left/right lungs, esophagus, heart, and spinal cord were retrieved from the clinical treatment plans. These contours were checked for quality and edited if necessary to ensure adherence to RTOG 1106 contouring guidelines., Data Format and Usage Notes: The CT images and RTSTRUCT files are available in DICOM format. The regions of interest were named according to the nomenclature recommended by American Association of Physicists in Medicine Task Group 263 as Lung&#95;L, Lung&#95;R, Esophagus, Heart, and SpinalCord. This dataset is available on The Cancer Imaging Archive (funded by the National Cancer Institute) under Lung CT Segmentation Challenge 2017 (http://doi.org/10.7937/K9/TCIA.2017.3r3fvz08)., Potential Applications: This dataset provides CT scans with well-delineated manually drawn contours from patients with thoracic cancer that can be used to evaluate auto-segmentation systems. Additional anatomies could be supplied in the future to enhance the existing library of contours., (© 2020 American Association of Physicists in Medicine.)

Background Stereotactic ablative radiotherapy (SABR) is effective for thoracic cancer and metastases; however, adverse effects are greater for central tumors. We evaluated factors affecting outcomes and toxicities after SABR for patients with primary lung and oligometastatic tumors. Patients and methods We retrospectively identified consecutive patients with centrally located lung tumors that were treated at our hospital from 2009-2016. The effects of patient, disease, and treatment-related parameters on local control (LC), overall survival (OS), and toxicity-free survival (TFS) were evaluated with multivariate analyses. Results Among 65 consecutive patients identified with 70 centrally located tumors, 20 tumors (28%) were reirradiated. Median (range) total dose for all tumors was 55 (30-60) Gy in 5 (3-10) fractions. Radiographic complete response was obtained in 43 lesions (61%). None of the analyzed factors were correlated with complete response. After a median follow-up of 57 (95% CI, 48-65) months, 10 tumors (14%) relapsed and 37 patients (57%) died; the actuarial 2- and 5-year OS rates were 52% and 28%, respectively. Median OS was significantly lower in patients with grade 3 or higher toxicity vs. lower toxicity (5 vs. 39 months; P < 0.001). Among 17 severe toxicities, 5 were grade 5, and 3 of them were reirradiated to the same field. Grade 3 to 5 TFS was lower with vs. without reirradiation (2-year TFS, 63% vs. 96%; P = 0.02). Conclusions Our study showed that modern SABR is effective for central lung tumors, and toxicities are acceptable. SABR for reirradiated central lung lesions and possibly for lesions abutting the tracheobronchial tree may result in higher risk of serious toxicities.

Background: Internal Target Volume (ITV) is one of the most common strategies to passively manage tumour motion in Radiotherapy (RT). The reliability of this approach is based on the assumption that the tumour motion estimated during pre-treatment 4D Computed Tomography (CT) acquisition is representative of the motion during the whole RT treatment. With the introduction of Magnetic Resonance-guided RT (MRgRT), it has become possible to monitor tumour motion during the treatment and verify this assumption. Aim of this study was to investigate the reliability of the ITV approach with respect to the treatment fraction time (TFT) in abdominal and thoracic lesions., Methods: A total of 12 thoracic and 15 abdominal lesions was analysed. Before treatment, a 10-phase 4DCT was acquired and ITV margins were estimated considering the envelope of the lesion contoured on the different 4DCT phases. All patients underwent MRgRT treatment in free-breathing, monitoring the tumour position on a sagittal plane with 4 frames per second (sec). ITV margins were projected on the tumour trajectory and the percentage of treatment time in which the tumour was inside the ITV (%TT) was measured to varying of TFT. The ITV approach was considered moderately reliable when %TT ≥ 90% and strongly reliable when %TT ≥ 95%. Additional ITV margins required to achieve %TT ≥ 95% were also calculated., Results: In the analysed cohort of patients, ITV strategy can be considered strongly reliable only for lung lesions with TFT ≤ 7 min (min). The ITV strategy can be considered only moderately reliable for abdominal lesions, and additional margins are required to obtain %TT ≥ 95%. Considering a TFT ≤ 4 min, additional margins of 2 mm in cranio-caudal (CC) and 1 mm in antero-posterior (AP) are suggested for pancreatic lesions, 3 mm in CC and 2 mm in AP for renal and liver ones., Conclusions: On the basis of the analysed cases, the ITV approach appears to be reliable in the thorax, while it results more challenging in the abdomen, due to the higher uncertainty in ITV definition and to the observed larger intra and inter-fraction motion variability. The addition of extra margins based on the TFT may represent a valid tool to compensate such limitations.

Background: Early screening and diagnosis of radiation-induced heart disease (RIHD) is difficult in patients with chest radiation exposure. sST-2 is involved in myocardial stress or injury. We evaluated the relationship between heart dose parameters and sST-2 changes in chest malignant tumor patients who received chest radiation., Methods: We prospectively collected thoracic malignancy cancer patients who had received chest radiotherapy. Heart dosimetry parameters were extracted from the treatment planning system. sST-2 was measured at baseline, the middle stage, and after radiotherapy (recorded as pre-ST-2, mid-ST-2, and post-ST-2). sST-2 change rate was calculated. Scatter plots showed the relationship between cardiac dose parameters and ST-2 change rate. Multiple regression was used to analyze the relationship between cardiac dose parameters and ST-2 change rate., Results: Totally, 60 patients were enrolled. The mean V 5 , V 10 , V 20 , V 30 , V 40 , and MHD was 60.93 ± 27.79%, 51.43 ± 25.44%, 39.17 ± 21.75%, 28.07 ± 17.15%,18.66 ± 12.18%, and 18.60 ± 8.63 Gy, respectively. The median M-LAD was 11.31 (IQR 3.33-18.76) Gy. The mean pre-ST-2, mid-ST-2, and post-ST-2 was 5.1 ± 3.8, 6.4 ± 3.9, and 7.6 ± 4.4, respectively. sST-2 was elevated with thoracic irradiation (P < .001). Multivariate linear regression analyses showed that V 5 , V 10 , V 20 , and MHD were independently and positively associated with ST-2 change rate (β = .04, .04, .04, and .10, respectively, all P < .05)., Conclusion: Serum sST-2 levels were elevated over time during radiotherapy. V 5 , V 10 , V 20 and MHD were independently and positively associated with the elevated ST-2 change rate., (© 2019 The Authors. Journal of Clinical Laboratory Analysis Published by Wiley Periodicals, Inc.)

Background: The role of adjuvant radiation therapy (RT) in the management of thoracic soft tissue sarcomas (STSs) remains unclear. We aimed to study the characteristics of patients with thoracic STS who received RT after surgical resection and investigate the impact of RT on survival outcomes., Methods: We queried National Cancer Database to identify patients with surgically resected thoracic STS from 2004 to 2012. Factors associated with receiving adjuvant RT were identified. Analyses were performed to identify prognostic factors and compare overall survival (OS) in both unmatched and propensity score-matched cohorts., Results: Overall, 1215 patients were identified, of whom 557 (45.8%) received adjuvant RT. Tumor grade (odds ratio [OR], 2.87; 95% confidence interval [CI], 2.18-3.77), tumor size (OR, 1.82; 95% CI, 1.36-2.42), and tumor margins (OR, 1.97; 95% CI, 1.43-2.72) were found to be significant predictors of receiving RT. Mean OS of patients receiving RT in the unmatched cohort was 91 months vs 88 months for patients who did not (P = .556). When adjusted for all variables, adjuvant RT was found to be associated with improved survival (hazard ratio, 0.79; 95% CI, 0.61-0.96). Survival analysis of the matched cohort also demonstrated improved survival with adjuvant RT (120 months vs 100 months; P = .02). Subgroup analysis in both the unmatched and matched cohorts showed patients with high-grade tumors more likely to benefit from adjuvant RT., Conclusions: This population-based analysis is the largest dataset of primary thoracic STSs to date and suggests significant survival benefit associated with adjuvant RT. The improvement in OS was more notable in patients with high-grade tumors. Randomized prospective studies are warranted to further understand the benefit of RT in this group., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: To ascertain the safety and efficacy of radioactive iodine-125 seed implantation (RISI) for the treatment of thoracic tumors., Methods: Clinical patients with primary or metastatic tumors in the chest treated with RISI were analyzed. The RISI process included the following stages: preoperative planning, template design and 3D printing, CT-guided RISI assisted by a template, and postoperative dosimetric verification. The prescribed dose was ≥ 80 Gy. The main analytic measures were the local control (LC) rate and toxicity., Results: From April 2015 to July 2018, a total of 92 patients, including 41 with lung cancer and 51 with lung metastases, were analyzed. The median lesion diameter was 5 cm. The median postoperative D90 was 142.6 Gy. The median follow-up was 10.7 months. The overall survival rates at 1 year and 3 years were 59.7% and 22.2%, respectively. The LC rates at 1 year and 3 years were 64.9% and 32.8%, respectively. The LC rates at 3 years for patients with D90 < 140 Gy and D90 > 140 Gy were 23.1% and 54.3%, respectively (P = 0.014). The LC rate of metastatic lung cancer was more favorable than that of primary lung cancer. The multivariate analyses showed that the dose and lesion type were independent factors for LC (P < 0.05). No factors were related to OS. The incidence of pneumothorax and hemoptysis was 35.8% and 3.2%, respectively. Few cases of radiotherapy-related toxicity effects were observed., Conclusions: RISI may be safe and efficacious and is associated with few complications during the treatment of thoracic tumors. If patients need local treatment and surgery or radiotherapy is not available, RISI could be considered.

Introduction: Contouring has become an increasingly important aspect of radiation therapy due to inverse planning, and yet is extremely time-consuming. To improve contouring efficiency and reduce potential inter-observer variation, the atlas-based auto-segmentation (ABAS) function in Velocity was introduced to ICON cancer centres (ICC) throughout Australia as a solution for automatic contouring., Methods: This paper described the implementation process of the ABAS function and the construction of user-defined atlas sets and compared the contouring efficiency before and after the introduction of ABAS., Results: The results indicate that the main limitation to the ABAS performance was Velocity's sub-optimal atlas selection method. Three user-defined atlas sets were constructed. Results suggested that the introduction of the ABAS saved at least 5 minutes of manual contouring time (P < 0.05), although further verification was required due to limitations in the data collection method. The pilot rollout adopting a 'champion' approach was successful and provided an opportunity to improve the user-defined atlases prior to the national implementation., Conclusion: The implementation of user-defined ABAS for head and neck (H&N) and female thorax patients at ICCs was successful, which achieved at least 5 minutes of efficiency gain., (© 2019 The Authors. Journal of Medical Radiation Sciences published by John Wiley & Sons Australia, Ltd on behalf of Australian Society of Medical Imaging and Radiation Therapy and New Zealand Institute of Medical Radiation Technology.)

Purpose of Review: This review describes the effects of radiotherapy (RT) on coronary artery disease, its mechanisms, and clinical and laboratory evidence and discusses ways to minimize radiation-induced coronary atherosclerosis., Recent Findings: Radiation-induced cardiac toxicity is known in patients undergoing thoracic RT. One of the damages occurs in the coronary arteries, with accelerated atherosclerosis manifesting decades later. There is clinical and laboratory evidence of coronary damage in retrospective studies, systematic reviews, and meta-analyses. Clinical studies have shown that RT cardiotoxicity occurs decades after radiation, regardless of chemotherapy, and may occur earlier in patients with pre-existing risk factors or disease. The pathogenesis of radiation-induced coronary artery disease is complex and multifactorial, including endothelial dysfunction, altered vascular tone, hemostatic imbalance, and inflammatory activation. Some factors are responsible, such as mean heart dose, RT chest site, patient position, techniques, and breathing maneuvers. There are approaches to reduce radiation-induced cardiac toxicity. Among them, besides the mentioned factors, metformin and anti-inflammatory agents can minimize coronary damage, with impact on morbidity and mortality.