International Thymic Malignancy Interest Group Research Articles

Re-evaluation and operative indications after induction therapy for thymic epithelial tumors.

Thymic epithelial tumors (TETs), encompassing thymoma and thymic carcinoma, represent a rare and heterogeneous group of thoracic malignancies with varying prognoses and treatment strategies. Surgical resection is the cornerstone of therapy for localized stages, but the management of locally advanced or unresectable TETs often involves induction therapy, including chemotherapy and/or radiation therapy, as a neoadjuvant approach aimed at downstaging the tumor to facilitate subsequent resection. This review synthesizes current knowledge on the re-evaluation process and operative indications following induction therapy for TETs, highlighting the pivotal role of accurate assessment in guiding surgical decisions and optimizing patient outcomes. Induction therapy's efficacy is contingent upon precise re-evaluation methods to accurately gauge treatment response and assess resectability post-therapy. This review discusses the various modalities employed in re-evaluation, including computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-CT (PET-CT), and the significance of tumor markers, underlining their strengths and limitations. The adoption of modified RECIST criteria for TETs by the International Thymic Malignancy Interest Group (ITMIG) underscores the necessity for standardized assessment guidelines to ensure consistency and reliability across studies and clinical practices. Furthermore, we explore the implications of induction therapy on surgical decision-making, emphasizing the criteria for determining the suitability of patients for surgical intervention post-therapy. The review addresses the challenges and future perspectives associated with the re-evaluation process, including the potential for advanced imaging techniques and the integration of molecular and genetic markers to enhance the precision of treatment response assessment. In conclusion, the re-evaluation of TETs post-induction therapy is a complex but critical component of the multidisciplinary management approach for these patients. Standardizing re-evaluation methodologies and incorporating novel diagnostic tools could significantly improve the prognostication and treatment stratification, ultimately enhancing the therapeutic outcomes for patients with advanced TETs.

Survival Outcome After Surgery in Patients With Thymoma Distant Recurrence

ObjectiveThe aim of this study is to describe characteristics and survival outcome of patients who underwent surgical treatment for distant thymoma relapse according to the definition of the International Thymic Malignancy Interest Group. MethodsData of patients affected by thymoma recurrence from four different institutions were collected and retrospectively reviewed. Patients with locoregional metastases who underwent nonsurgical therapies and with incomplete data on follow-up were excluded. According to the International Thymic Malignancy Interest Group distant recurrence definition, patients with recurrence due to hematogenic localization were included. Clinical and pathologic characteristics were described using descriptive statistics, whereas survival outcome was calculated using Kaplan-Meier curves and Cox regression analysis. ResultsThe analysis was conducted on 40 patients. A single localization was present in 13 patients, the relapse was intrathoracic in 28 cases (70%), and lung involvement was found in 26 cases. The liver was operated in seven cases, whereas other kinds of abdominal involvement were detected in eight cases. Adjuvant treatment was administered in 22 cases (55%).Five- and 10-year overall survival (OS) were 67% and 30%, respectively. Univariable analysis identified as significant favorable factor a low-grade histology (A, B1, B2): five-year OS at 92.3% versus 53.3% in high-grade (B3–C) (p = 0.035). Site of recurrence and number of localization did not influence the prognosis, but in patients with adjuvant therapy administration, there was a survival advantage also if not statistically significant: five-year OS 84.8% versus 54.5% in patients without adjuvant therapy (p = 0.101).Multivariable analysis confirmed as independent prognostic factor low-grade histology: hazard ratio = 0.176, 95% confidence interval 0.042–0.744, p = 0.018. ConclusionsOur study revealed a good survival outcome in patients who underwent surgery for distant thymoma recurrence, independently from the number and site of the relapse localization. Patients with A, B1, or B2 histology presented a significantly better survival than patients with B3-C.

International reproducibility study of thymic epithelial tumors staging: pT stage is an issue. proposals for improvement. A RYTHMIC/ITMIG study

IntroductionPathologists are staging thymic epithelial tumors (TET) according to the 8th UICC/AJCC TNM system. Within the French RYTHMIC network, dedicated to TET, agreement on pathologic tumor stage (pT) among the pathology panelists was difficult. The aim of our study was to determine the interobserver reproducibility of pT at an international level, to explore the source of discrepancies and potential interventions to address these. MethodsAn international panel of pathologists was recruited through the International Thymic Malignancy Interest Group (ITMIG). The study focused on invasion of mediastinal pleura, pericardium, and lung. From a cohort of cases identified as challenging within the RYTHMIC network, we chose a series of test and validation cases (n = 5 and 10, respectively). ResultsReproducibility of the pT stage was also challenging at an international level as none of the 15 cases was classified as the same pT stage by all ITMIG pathologists. The agreement rose from slight (κ = 0.13) to moderate (κ = 0.48) between test and validation series. Discussion among the expert pathologists pinpointed two major reasons underlying discrepancies: 1) Thymomas growing with their “capsule” and adhering to the pleurae, pericardium, or lung were often misinterpreted as invading these structures. 2) Recognition of the mediastinal pleura was identified as challenging. ConclusionOur study underlines that the evaluation of the pT stage of TET is problematic and needs to be addressed in more detail in an upcoming TNM classification. The publication of histopathologic images of landmarks, including ancillary tests could improve reproducibility for future TNM classifications.

TNM Staging System in Thymoma: A Critical Appraisal?

Thymomas are rare tumors of the anterior mediastinum with peculiar clinical and pathological features. They have been deeply analyzed by pioneer authors, who strictly linked their name to the main pathological and staging classifications. Before the latest edition of the WHO classification of thymic epithelial tumors, the history of thymoma pathological classification inherited the name of the pathologists who systematically addressed the issue, from Levine-Rosai to Muller-Hermelink. Similarly, the thymoma staging system is intimately related to the name of two surgeons, Masaoka and Koga, who historically dealt with this disease. More recently, the traditional tumor-nodes-metastasis (TNM) system has been developed for the staging of this condition, in a rational attempt to put thymomas in conformity with the other solid tumors. The efforts of the International Thymic Malignancies Interest Group (ITMIG) and the Thymic Domain of the Staging and Prognostic Factors Committee (TD-SPFC) of the International Association for the Study of Lung Cancer (IASLC) resulted in the TNM classification of thymic tumors, which have been included in the eighth edition of the American Joint Committee on Cancer's (AJCC) Cancer Staging Manual. Herein, we report a narrative review of the evolution of the thymic epithelial tumors (TET) staging system and present a critical appraisal of the actual TNM classification compared with the historical Masaoka-Koga classification, with special focus on the proposal for the ninth edition of the TNM, expected in 2024.

Approach to Imaging of Mediastinal Masses.

Mediastinal masses present a diagnostic challenge due to their diverse etiologies. Accurate localization and internal characteristics of the mass are the two most important factors to narrow the differential diagnosis or provide a specific diagnosis. The International Thymic Malignancy Interest Group (ITMIG) classification is the standard classification system used to localize mediastinal masses. Computed tomography (CT) and magnetic resonance imaging (MRI) are the two most commonly used imaging modalities for characterization of the mediastinal masses.

The International Association for the Study of Lung Cancer Thymic Epithelial Tumors Staging Project: An Overview of the Central Database Informing Revision of the Forthcoming (Ninth) Edition of the TNM Classification of Malignant Tumors

IntroductionIn 2014, a TNM-based system for thymic epithelial tumors was proposed. The TNM stage classification system was published as a result of a joint project from the International Association for the Study of Lung Cancer and the International Thymic Malignancy Interest Group for the eighth edition of the American Joint Commission on Cancer and the Union for International Cancer Control stage classification system. The Thymic Domain of the Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer received the mandate to make proposals for the ninth edition of the TNM stage classification. MethodsA central thymic database was collected by the Cancer Research And Biostatistics with the contribution of the major thymic associations in the world. ResultsA total of 11,347 patients were collected. Submitting organizations were the following: Japanese Association for Research in the Thymus, European Society of Thoracic Surgeons, Chinese Alliance for Research in Thymoma, Korean Association for Research in the Thymus, International Thymic Malignancy Interest Group, and Réseau tumeurs THYMiques et Cancer. Additional contributions came from centers in the United States, United Kingdom, Turkey, Australia, Spain, and Italy. A total of 9147 cases were eligible for analysis. Eligible cases for analysis came from Asia and Australia (5628 cases, 61.5%), Europe (3113 cases, 34.0%), and North America (406 cases, 4.4%). ConclusionsThis report provides an overview of the database that has informed the proposals for the updated T, N, and M components and the stage groups for the ninth TNM of malignant tumors.

The International Association for the Study of Lung Cancer Thymic Epithelial Tumor Staging Project: A Re-Assessment of the International Thymic Malignancy Interest Group/International Association for the Study of Lung Cancer Lymph Node Map for Thymic Epithelial Tumors for the Forthcoming Ninth Edition of the TNM Classification of Malignant Tumors

IntroductionA lymph node map is the pillar on which accurate assignment and documentation of nodal classification stands. The International Thymic Malignancy Interest Group created the first map for thymic epithelial malignancies in conjunction with the eighth edition of the TNM classification, representing the first official TNM classification of thymic epithelial malignancies. The map was based on clinical experience and published studies, but it was largely empirical because of limited available data. Dissemination of the map and implementation of a standard thymic stage classification across the world in 2017 have provided more consistent and granular data. MethodsMore than twice as many cases of node involvement are available for analysis in the current database compared with that of the eighth edition database, allowing validation of many aspects of the eighth edition map. This article details the process and considerations for refinement of the thymic map for the ninth TNM used by the Thymic Domain of the Staging and Prognostic Factors Committee of the International Association for the Study of Lung Cancer. The committee evaluated a large international collaborative data set, published anatomical and clinical studies pertaining to lymph node spread from thymic epithelial tumors, in conjunction with the analysis underlying refinements of the TNM components for the ninth edition TNM classification. ResultsThe node map boundaries of the N1 and N2 categories remain unchanged. Visual clarifications have been added to the nomenclature of nodal stations within these regions. ConclusionsOn the basis of the recommendation to keep the N component unchanged for the ninth edition TNM classification, the lymph node map remains unchanged as well; however, clarifications have been added to facilitate clinical use.

Giant middle mediastinal lesions: when tumor size correlates with mesenchymal origin-a retrospective single-center analysis.

The International Thymic Malignancy Interest Group (ITMIG) proposed an internationally accepted division of the mediastinum into three compartments based on computed tomography (CT): anterior (prevascular), middle (visceral) and posterior (paravertebral) compartment. There is no generally accepted definition for the term "giant" when applied to middle mediastinal lesions. We defined the term "giant" and described our surgical experience in treating patients with giant lesions of the middle mediastinum. CT imaging of patients operated in our center from January 2016 to August 2021 for mediastinal lesions was reviewed. Lesions were categorized to one of the ITMIG-defined compartments. Lesion size at diagnosis was measured at its largest diameter on axial CT imaging. Giant middle mediastinal lesions were defined as lesions having a size ≥90th percentile of our middle mediastinal lesion cohort. Patients with giant middle mediastinal lesions were further analyzed. Thirty-six patients (23%) had lesions located in the middle mediastinal compartment. Most common diagnoses were mediastinal cysts (n=10, 28%), metastatic lesions (n=6, 17%), lymphomas (n=5, 14%), and sarcomas (n=3, 8%). Ninetieth percentile lesion size was 73 mm. As per definition, four patients had giant middle mediastinal lesions. All these four lesions were of mesenchymal origin including oesophageal leiomyoma, synovial sarcoma, leiomyosarcoma and undifferentiated round cell sarcoma. Resection was performed through posterolateral thoracotomy or sternotomy, with or without cardiopulmonary bypass. The term "giant" could be defined as a mass larger or equal to 73 mm. This definition selected specifically lesions with mesenchymal origin and may therefore guide diagnostic algorithm and patient management.

Imaging evaluation of thymic tumors.

An integral part of managing patients with thymoma and thymic carcinoma is imaging. At diagnosis and staging, imaging helps demonstrate the extent of local invasion and distant metastases which allows the proper stratification of patients for therapy. For decades, the predominant staging system for thymic tumors was the Masaoka-Koga staging system. More recently, however, the International Association for the Study of Lung Cancer, the International Thymic Malignancies Interest Group (ITMIG), the European Society of Thoracic Surgeons, the Chinese Alliance for Research on Thymomas, and the Japanese Association of Research on Thymus partnered together to develop a tumor-node-metastasis (TNM) staging system specifically for thymic tumors based on a retrospective database of nearly 10,000 patients. The TNM 8th edition defines specific criteria for thymic tumors. Imaging also serves to assess treatment response and detect recurrent disease after various treatment modalities. The Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 is currently used to assess response to treatment. ITMIG recommends certain modifications to RECIST version 1.1, however, in thymic tumors due to unique patterns of spread. While there is often overlap, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT) characteristics can help differentiate thymoma and thymic carcinoma, with newer CT and MRI techniques under evaluation showing encouraging potential.

Multimodality imaging of mediastinal masses and mimics.

A wide variety of neoplastic and nonneoplastic conditions occur in the mediastinum. Imaging plays a central role in the evaluation of mediastinal pathologies and their mimics. Localization of a mediastinal lesion to a compartment and characterization of morphology, density/signal intensity, enhancement, and mass effect on neighboring structures can help narrow the differentials. The International Thymic Malignancy Interest Group (ITMIG) established a cross-sectional imaging-derived and anatomy-based classification system for mediastinal compartments, comprising the prevascular (anterior), visceral (middle), and paravertebral (posterior) compartments. Cross-sectional imaging is integral in the evaluation of mediastinal lesions. Computed tomography (CT) and magnetic resonance imaging (MRI) are useful to characterize mediastinal lesions detected on radiography. Advantages of CT include its widespread availability, fast acquisition time, relatively low cost, and ability to detect calcium. Advantages of MRI include the lack of radiation exposure, superior soft tissue contrast resolution to detect invasion of the mass across tissue planes, including the chest wall and diaphragm, involvement of neurovascular structures, and the potential for dynamic sequences during free-breathing or cinematic cardiac gating to assess motion of the mass relative to adjacent structures. MRI is superior to CT in the differentiation of cystic from solid lesions and in the detection of fat to differentiate thymic hyperplasia from thymic malignancy.

International Thymic Malignancy Interest Group Classification – The Future of Mediastinal Mass Evaluation using Multidetector Computed Tomography

Background: The diagnosis of mediastinal masses is a demanding task as it is like Pandora’s box with diverse masses. Multidetector computed tomography (MDCT), along with intravenous contrast, is the diagnostic technique of choice to diagnose mediastinal masses. Hence, the International Thymic Malignancy Interest Group (ITMIG) uses MDCT as a gold standard for defining mediastinal compartments. Aim and Objectives: The purpose of this study was to ascertain characteristics, the accurate extension of mediastinal masses, and its distribution according to classification by ITMIG and to correlate the fine-needle aspiration cytology/biopsy diagnosis to the findings of the computed tomography (CT) scan where ever possible. Materials and Methods: The present study was conducted at the Radiodiagnosis Department of AVBRH, a Teaching Hospital of DMIHER, Sawangi (Meghe) Wardha. It was a prospective cross-sectional study. A purposive convenience sampling method was used with a sample size of 100 participants needed for 2 years. Results: In the study population, the predominant (63%) participants were male, and the remaining 37 (37.00%) participants were female. Fifteen (15.00%) lesions were in prevascular, 55 (55.00%) were in visceral, 15 (15.00%) were in paravertebral, 8 (8.00%) involved Prevascular + Visceral, 7 (7.00%) lesions involved all three compartments, i.e., Prevascular + Visceral + Paravertebral localization. In the present study, in 94.73% of the masses, the same diagnosis was made by both CT and holoprosencephaly. In 5.27% of the masses, the diagnosis was different. The total diagnostic accuracy was 100% (95% confidence interval 93.73%–100%). Conclusion: CT has a cardinal part in the assessment of different masses in the mediastinum in regards to their characterization, distribution, and distinguishing malignant and benign lesions. The novel mediastinal division system introduced by ITMIG is intended to facilitate uniform communication between health-care professionals and radiologists at cross-sectional imaging.

Lesions of the prevascular mediastinum

Mediastinal masses are agroup of heterogenous lesions which may be acoincidental finding or present with symptoms. More than half of mediastinal lesions are located in the prevascular mediastinum. As these tumors are not often encountered in clinical routine, making adiagnosis with ahigh degree of confidence may seem challenging. The latest computed tomography (CT)-based classification of the mediastinal compartments by the International Thymic Malignancy Interest Group (ITMIG) moves away from earlier radiograph-based classification systems and helps to reliably classify tumors based on location, although in some cases the lesion can occupy more than one compartment. Radiology plays an important role in the evaluation of anterior mediastinal lesions. Although in some cases imaging features alone allow adiagnosis to be made; in other cases knowledge of important radiological features and their analysis in the context of patient factors like age and duration of symptoms can help to narrow down the differential diagnosis, avoid unnecessary workup, and guide further steps. Computed tomography (CT) is central for the characterization of mediastinal masses in clinical routine. In some situations, like in the case of thymic cysts or thymic hyperplasia, magnetic resonance imaging (MRI) can be used as anoninvasive problem-solving tool.

Mediastinum-new compartment classification

Mediastinal masses are common and comprise aheterogeneous spectrum of disorders. Correct diagnosis has prognostic and therapeutic consequences, which is why precise localization of lesions and interdisciplinary management are essential in clinical practice. This article describes traditional divisions of mediastinum lesions and presents the new classification based on cross-sectional imaging, which was developed by the International Thymic Malignancy Interest Group (ITMIG). Which divisions of the mediastinum have been used so far and how does the division developed by the ITMIG differ? What are the advantages of the new mediastinal classification? Comparison of the previously used mediastinal classification with the new mediastinal classification developed by ITMIG and visualization of the respective methods. In addition, pathologies typical for the respective compartments are explained. The traditional compartmentalization of the mediastinum into an anterior, middle, and posterior mediastinum is not clearly defined and may lead to confusing interdisciplinary communication. Since these classifications are mostly based on projection radiographs, the proposed three-dimensional classification of the ITMIG is adevelopment that suits the modern clinical workflow and promotes standardization. The three mediastinal compartments should thus be termed prevascular, visceral, and paravertebral.

MA10.04 Long-term Follow-up Study of Thymic Epithelial Tumors. Report of the Updated Nation-wide Database in Japan

International Thymic Malignancy Interest Group (ITMIG) and IASLC started the global database project in the 2010’s, and finally, established a large-scale database of more than 10,000 patients. TNM-based staging system proposed by IASLC Staging and prognostic factor Committee Thymic domain (SPFC-TD) was approved by UICC version 8 in 2016. Japanese Association for Research of the Thymus (JART) established Japanese nation-wide database of approximately 3000 cases in 2013 and contributed to IASLC Staging project.

Topography of the mediastinum departments in the X-ray image in the context of differentiation of volume mediastinal formations

The division of the mediastinum into specific departments is necessary for targeted differential diagnosis of mediastinal masses in imaging studies and planning biopsies and surgical procedures. The majority of radiological classifications are based on arbitrary marks that are conventionally labeled on a lateral chest radiograph. At present, the use of multislice computed tomography (MSCT) with a wide range of post-processing of axial tomographic images has become the gold standard for visualization of diseases of the chest organs. A new scheme based on cross-sectional imaging during MSCT has been developed by the International Thymic Malignancy Interest Group (ITMIG) and adopted as the standard. Using the example of diagnosing some solid formations (own clinical and radiological observations), this article sets out various classifications of the mediastinal sections according to the radiograph of the lungs in the lateral projection, which are the place of priority localization of a number of pathological formations, which greatly simplifies the identification of this pathology.

Pediatric mediastinal masses.

Mediastinal masses are categorized based on the International Thymic Malignancy Interest Group (ITMIG) classification into prevascular, visceral and paravertebral compartments. The schema is based on cross-sectional imaging, mainly CT, and helps with generating a differential diagnosis based on location of the mass. Up to half of all pediatric mediastinal tumors are malignant. In this review we describe mediastinal masses that are relevant to the pediatric population, as well as the role of MR imaging of mediastinal masses and its advantages.

Imaging evaluation of the pediatric mediastinum: new International Thymic Malignancy Interest Group classification system for children.

Mediastinal masses are commonly identified in the pediatric population with cross-sectional imaging central to the diagnosis and management of these lesions. With greater anatomical definition afforded by cross-sectional imaging, classification of mediastinal masses into the traditional anterior, middle and posterior mediastinal compartments - as based on the lateral chest radiograph - has diminishing application. In recent years, the International Thymic Malignancy Interest Group (ITMIG) classification system of mediastinal masses, which is cross-sectionally based, has garnered acceptance by multiple thoracic societies and been applied in adults. Therefore, there is a need for pediatric radiologists to clearly understand the ITMIG classification system and how it applies to the pediatric population. The main purpose of this article is to provide an updated review of common pediatric mediastinal masses and mediastinal manifestations of systemic disease processes in the pediatric population based on the new ITMIG classification system.

Mediastinal lesions : The most common pathologies in chest X-rays and their correlations in computed tomography

Many pathologies of the mediastinum can be diagnosed using standard radiographs. Correlation of radiographic findings with computed tomography (CT) is instructive for abetter understanding and can help improve detection rates of mediastinal lesions. To identify the most common mediastinal lesions and to correlate their features in chest radiographs and CT. The International Thymic Malignancy Interest Group (ITMIG) classification in the anterior, middle, and posterior mediastinum is based on anatomic landmarks. Used as atool to characterize mediastinal lesions this classification is applied in this article. The most common lesions include mediastinal goiter, germ cell and thymic neoplasms in the anterior mediastinum, lymphadenopathy in the middle mediastinum, and neurogenic neoplasms in the posterior mediastinum. Other lesions of neoplastic or non-neoplastic origin can be distinguished in the three compartments and should be considered in the differential diagnosis. Knowledge of the most common pathologies in the three mediastinal compartments can accelerate differential diagnosis. Understanding the normal mediastinal lines is key in anatomic localization and detection of many lesions in chest radiographs.

Impact of the TNM staging system for thymoma.

BackgroundMasaoka-Koga staging system remains the most frequently applied clinical staging system for thymic malignancy. However, the International Association for the Study of Lung Cancer (IASLC)/International Thymic Malignancy Interest Group (ITMIG) proposed a tumor-node-metastasis (TNM) staging system in 2014. This study aims to evaluate its impact on stage distribution, clinical implementation, and prognosis for thymomas.MethodsWe performed a single institution, retrospective analysis of 245 consecutive patients who underwent surgical resection for thymoma. 9 patients with thymic carcinoma were excluded. No patients were lost to follow up. Kaplan-Meier survival analysis was used to calculate overall survival.ResultsMedian age was 62 years; 129 patients (53%) were female. The median overall survival was 158 months (range, 108–208 months), and disease-free survival 194 months (range, 170–218 months). At the end of follow up 63 patients were dead. Early Masaoka-Koga stages I (n=74) and II (n=129) shifted to the IASLC/ITMIG stage I (n=203). 8 patients were down staged from Masaoka-Koga stage III to IASLC/ITMIG stage II because of pericardial involvement. Advanced stages III (Masaoka-Koga: n=30; IASLC/ITMIG: n=22) and IV (Masaoka-Koga: n=12; IASLC/ITMIG: n=12) remained similar and were associated with more aggressive WHO thymoma histotypes (B2/B3). Masaoka-Koga (P=0.004), IASLC/ITMIG staging (P<0.0001) and complete surgical resection (P<0.0001) were statistically associated with survival. At multivariate analysis only R status was an independent prognostic factor for survival.ConclusionsThe proportion of patients with stage I disease increased significantly when IASLC/ITMIG system used, whilst the proportion with stages III and IV were similar in both systems. Completeness of resection, Masaoka-Koga and the IASLC/ITMIG staging system are strong predictors of survival. The TNM staging system is useful in disease management and a strong predictor of overall survival.

External Validation of Pulmonary Toxicity Risk Model for Ultracentral Lung Tumors

Pulmonary toxicity attributed to the proximal bronchial tree (PBT) is dose-limiting in stereotactic body radiation therapy (SBRT) for central lung tumors. The toxicity is of particular concern in ultracentral lesions, which are defined as the gross tumor volume abutting the PBT, esophagus, or other mediastinal structures. In this work we tested published pulmonary toxicity models associated with dose to the airway structures after SBRT for ultracentral tumors in an independent institutional cohort of patients.The PubMed database was scrutinized for toxicity models evaluating pulmonary and airway toxicity for SBRT or hypofractionated radiation treatment for central tumors in the lung. The following search term criteria were used: (central) AND (lung tumor) AND (normal tissue complication probability) AND (radiation). Identified models were explored in all patients with ultracentral lung tumors treated between 2008 and 2017 at one large center (N = 88). This cohort included 60% primary lung and 40% metastatic patients that had been treated to 45 Gy in 5 fractions (fx), 50 Gy in 5 fx, 60 Gy in 8 fx, or 60 Gy in 15 fx. 16% of the patients received anti-VEGF therapy, which as previously shown, was associated with higher incidence of grade 5 hemorrhage.A total of six NTCP models were identified from work by Tekatli et al 2018. Of these, three models were for ≥grade 3 and three for grade 5 toxicity and included bronchial max dose, V60, V100, and V130. Clinical pulmonary toxicity consisted of radiation pneumonitis, atelectasis due to main stem bronchus occlusion, and/or hemoptysis. The pulmonary toxicity rate was 15% and 8% for ≥grade 3 toxicity and grade 5 toxicity, respectively, in the original study. Within the independent cohort, the corresponding values were 18% and 10%. Two maximum dose models were shown to be valid in our institutional dataset; other models failed this validation test. The model was made more robust by expanding the max dose region of the bronchial volume by focusing on the max dose to 0.1 cm3, 1 cm3 and 3 cm3. The max dose (0.1 cm3) model had improved performance with increased steepness. Generally, models from literature underestimated our institutional complication rates.Pulmonary toxicity models for central tumors were identified from one study and explored within an independent cohort. The models derived from primarily central lung tumors systematically underestimated the pulmonary toxicity rate in the solely ultracentral tumor cohort, possibly also due to anti-VEGF therapy used in the independent cohort. A modified model from the best-performing max dose model was designed, and this model could be utilized for rationally constructed airways constraints in ultracentral patients treated with SBRT or hypofractionation.I. Chen: None. M. Thor: None. A.J. Wu: Research Grant; CivaTech Oncology, Inc. Honoraria; 1199SEIU. Consultant; AstraZeneca, MORE Health. Advisory Board; Simphotek, Inc. Travel Expenses; AlphaTau Medical. Stock; Simphotek, Inc. A. Iyer: None. A. Apte: None. A. Rimner: Research Grant; Varian Medical Systems, Boehringer Ingelheim, Astra Zeneca, Pfizer, Merck. Consultant; MoreHealth. Advisory Board; Boehringer Ingelheim, Astra Zeneca, Merck; International Thymic Malignancies Interest Group, International Mesothelioma Interest Group. D.R. Gomez: Research Grant; Merck, AstraZeneca. Honoraria; BMS, Varian, Research to Practice. Speaker's Bureau; Merck. Advisory Board; AstraZeneca, Olympus. J.O. Deasy: Research Grant; Varian Corp., NIH, Breast Cancer Research Foundation. Stock; Paige.AI; AAPM.A. Jackson: None.