Clinical Significance of Tumor Disappearance Ratio in EGFR-Mutant Lung Adenocarcinoma with Brain Metastases: A Case Series

Clinical Significance of Tumor Disappearance Ratio in EGFR-Mutant Lung Adenocarcinoma with Brain Metastases: A Case Series | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Clinical Significance of Tumor Disappearance Ratio in EGFR-Mutant Lung Adenocarcinoma with Brain Metastases: A Case Series Firman Adi Prasetyo, Fierly Hayati This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7226145/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Among lung cancer subtypes, lung adenocarcinoma is the most frequently diagnosed histologic form and is commonly impacted by EGFR mutations. Tumor disappearance ratio (TDR) has been proposed as a prognostic marker. A decreased TDR tends to be linked with more invasive pathological characteristics, including pleural and lymphovascular involvement and advanced tumor stage. Notably, chest CT findings in patients with TDR ≤ 75% often revealed micropapillary or solid patterns that corresponded with higher invasiveness. Case presentation: We reported three cases of Lung Adenocarcinoma with TDR < 75% and CNS Metastases. All of the patient’s first CXR only shows consolidation but Chest CT and Histopathology confirm with Lung Adenocarcinoma EGFR mutation. All of those patients had neurology complaints as first symptoms rather than respiratory symptoms. First, Female 69 years old complained of chronic headache, then the patient performed brain MRI results show the cerebellar metastatic process. After that, the patient underwent chest CT show lung mass with TDR 11%. Then the patient has lower respiratory tract infection and sepsis with WBC 14.710 and procalcitonin 7,76 ng/ml. The patient died because of sepsis after 7 days of treatment. Second, Male 49 years old with right hemianesthesia. The patient complained of numbness and tingling of his right limb, the patient performed a brain MRI and show as brain metastasis. After that, the patient underwent chest CT show lung mass with TDR 33%. Then patient underwent for chemotherapy. After 10 days, patient has dyspnea and CXR show right pleural effusion. Then patient had thoracocentesis but respiratory failure still existed and patient died. Last case, Male 48 years old with a seizure, whole body spasm and eyes glancing upwards. First, patient was diagnosed as meningioma and performed brain surgery. The histopathology result show that metastatic adenocarcinoma from the lung. The patient underwent chest CT show lung mass with TDR 33%. Then patient underwent chemotherapy and radiotherapy, the patient had success for the CT evaluation as a partial response. Conclusion Low TDR value correlate with a vascular invasion that present as Brain Metastases in Lung Adenocarcinoma with EGFR mutation. Tumor Disappearance Ratio Lung Adenocarcinoma EGFR Mutation CNS Metastases Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 INTRODUCTION Representing 18% of all cancer cases, lung cancer is among the most frequent non-hematologic malignancies, predominantly affecting males with a median age of 70. Lung adenocarcinoma (LAD) stands as the most common histological subtype in non-small cell lung cancer (NSCLC), influenced by genetic mutations in EGFR, KRAS, and ALK. Adenocarcinoma now accounts for about half of all lung cancer diagnoses, being especially prevalent in females and non-smokers. Usually arising in the lung periphery, these tumors are often asymptomatic. Despite their slow growth pattern, adenocarcinomas are known for early metastatic potential. Radiographically, they appear as solitary nodules or masses with irregular margins such as spiculated or lobulated edges. CT imaging commonly reveals ground-glass opacities around the tumor, and in about 20% of cases, a pneumonia-like consolidation may also be present, occasionally accompanied by nodules in other lobes. ( 1 , 2 ) LAD characterized by ground-glass opacities (GGO) typically demonstrates a favorable prognosis, with pathology frequently revealing limited invasion. The tumor disappearance ratio (TDR) has gained recognition as a prognostic parameter. In tumors measuring 2 cm or less, a low TDR correlates with greater pathological invasiveness, including pleural and lymphovascular invasion, as well as more advanced pathological stages. Moreover, individuals with lower TDR tend to experience shorter recurrence-free and overall survival durations. ( 3 ) Tumor infiltration lymphocytes (TILs) play a pivotal role in the body’s immune defense against malignancies. In GGO-pattern LAD, tumors with high consolidation were found to contain more TILs than those with lower consolidation. LADs that lack solid components pathologically identified as adenocarcinoma in situ (AIS) exhibit reduced immune activity against tumor cells. In advanced LAD, EGFR wild-type tumors had increased CD8 + TIL infiltration and greater PD-L1 expression compared to tumors with EGFR mutations. The importance of detecting EGFR mutations in LAD has grown in recent years due to the superior clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) over standard chemotherapy in appropriately selected cases ( 1 , 4 ) There is variation in the reported cut-off values for the solid component ratio in lung tumors. Wu et al. identified a TDR of ≤ 75% as an independent risk factor associated with reduced 5-year disease-free survival (DFS) and a trend toward unfavorable overall survival (OS) after resection. Prior literature has also emphasized that the proportion of solid parts or GGO features may serve as important indicators of prognosis, with relevant concepts including the consolidation-to-tumor ratio (CTR), GGO ratio, and TDR. Hattori et al. demonstrated that patients with tumors ≤ 1 cm exhibiting GGO on CT had improved DFS. Similarly, the Japan Clinical Oncology Group 0201 (JCOG 0201) found that adenocarcinomas measuring ≤ 2 cm with a CTR ≤ 25% were associated with minimally invasive pathological profiles. Other research supports a 50% threshold for either the CTR or the GGO ratio. ( 3 , 5 , 6 ) CASE PRESENTATION We reported three cases of Lung Adenocarcinoma EGFR mutation with TDR < 75% and CNS Metastase. All of the patient’s first CXR only show consolidation but Chest CT and Histopathology confirm with Lung Adenocarcinoma EGFR mutation. All of those patients had neurology complaint as first symptoms rather than respiratory symptoms. Case 1 Female 69 years old non-smoker with Headache. The patient complained of chronic headache. There is no fever, no cough, no dyspnea. Then the patient performed brain MRI result show the cerebellar metastatic process (Figs. 3 and 4 ). After that, the patient underwent chest xray that only show consolidation in right paracardial (Fig. 1 ) but chest ct show lung mass (Fig. 2 ) followed by histopathology examination result as lung adenocarcinoma with EGFR mutation. Then the patient has lower respiratory tract infection and sepsis with WBC 14.710 and Procalcitonin 7,76 ng/ml. Patient died because of sepsis after 7 days of treatment. Case 2 Male 49 years old non-smoker with right hemianesthesia. The patient complain with numbness and tingling of his right limb, there is no headache, no dyspnea, no chough nor seizure. Then patient performed brain MRI and show as brain metastase (Fig. 7 ). After that, the patient underwent chest xray that only show consolidation in left parahilar (Fig. 5 ) but chest ct (Fig. 6 ) show lung mass followed by histopathology examination result as lung adenocarcinoma with EGFR mutation. Then patient underwent for chemotherapy. After 10 days, patient has dyspnea and chest xray show right pleural effusion. Then patient had thoracocentesis but respiratory failure still exist and patient dead. Case 3 Male 48 years old non-smoker with seizure. The patient had seizure, whole body spasm and eyes glancing upwards. First, patient was diagnosed as meningioma and performed brain surgery. The histopathology result show that metastatic adenocarcinoma from lung (Fig. 11 ). Then patient underwent chest xray with consolidation at right suprahilar (Fig. 8 ) followed by histopathology examination result as lung adenocarcinoma with EGFR mutation. Then patient underwent chemotherapy and radiotherapy, the patient had success for the ct evaluation as partial response. Table 1 Summarize TDR Cases Case Clinical Information TDR Staging EGFR mutation CNS Metastaes Case 1 Female 69 years old with chronic headache 11% St IVb (T2N3M1c) Exon 20 Cerebellar Case 2 Male 49 years old with right hemianesthesia 33% St IVb (T2N3M1c) Exon 19 Cerebral Case 3 Male 48 years old with seizure 33% St IVa (T1cN1M1b) Exon 18,19,20,21 Cerebral DISCUSSION Lung Adenocarcinoma with EGFR mutation are strong correlation with Brain metastase. These three cases (Table 1 ) have Brain metastase which two cases manifest as cerebral metastase and one case manifest as cerebellar metastase. Histology and disease stage of the initial lung cancer are among the major determinants of brain metastasis formation. Furthermore, the position of the primary tumor plays a role, as centrally located lesions appear more likely to metastasize to the brain. This statement only suitable with one case that location in central perihilar, but the others location are in peripheral. ( 8 ) Ortiz AFH et al. (2022) conducted an investigation involving 10,355 NSCLC patients to identify CT and clinical markers linked with EGFR mutation status. Their analysis revealed that GGO, air bronchogram, vascular convergence, pleural retraction, non-smoking status, and being female were independently associated with a higher likelihood of EGFR mutations in lung adenocarcinoma. This conclusion is supported by three cases presenting these radiological features alongside non-smoking history; however, two of the patients were male (aged 40–50) and one was a 69-year-old female. Supporting meta-analyses have similarly reported that air bronchogram, spiculated edges, and GGO are dominant CT characteristics frequently observed in EGFR-mutated adenocarcinomas. Wu et. al (2021) analyzed pre-surgical focused on clinical lymph node and distant metastatic status. None of the patients with a TDR > 75% demonstrated nodal or distant spread. In contrast, 31.0% of patients with TDR ≤ 75% presented with either lymph node involvement or distant metastasis, and 27.6% had distant metastasis specifically. Tumor cells can infiltrate blood or lymphatic vessels, travel through circulation, and colonize new sites. Remarkably, the angiogenic switch may be activated even in tumors under 1 cm in size. Pathologically, most TDR ≤ 75% cases on chest CT revealed micropapillary or solid components, which correlated with increased invasiveness in the solid portions visible on imaging. Tumor Disappearance Ratio (TDR) of the three cases are below 75% which is suitable with previous studies that low TDR correlated to more pathological invasiveness such as pleural invasion, lymphovascular invasion, and advanced pathological staging. Two cases have TDR of 33% (Figs. 6 and 9 ) and one cases has TDR of 11% (Fig. 2 ). All of these cases have advanced pathological staging with CNS metastases. One case has progressive pleural invasion as pleural effusion. CNS metastases continue to pose a major threat to patients with advanced NSCLC, significantly impairing neurological function, cognitive performance, and survival outcomes. It is estimated that approximately 30–40% of patients with advanced NSCLC develop metastasis to the central nervous system. The presence of specific tumor genomic alterations, particularly EGFR or ALK driver mutations, has been associated with a greater likelihood of brain metastases in these patients. ( 7 , 8 ) It has been reported that exon 21 EGFR mutations are more commonly associated with tumors exhibiting a greater extent of GGO, while exon 19 mutations are typically found in tumors that are smaller in size and demonstrate pleural retraction. Two cases have a mutation in exon 21 but no difference in GGO with the same TDR 33% in one case mutation in exon 19. Two cases have a mutation in exon 19 which is suitable with the meta-analysis result by presence of pleural retraction. The meta-analysis studies also state that individuals from Asia have an increase prevalence of EGFR mutation in NSCLC. CONCLUSION Low TDR value correlate with vascular invasion that presence as CNS Metastase in Lung Adenocarcinoma with EGFR mutation. The most frequent CT patterns associated with lung adenocarcinoma EGFR mutation are air bronchogram, spiculated margins and GGO. The characterization in LAD with EGFR mutation correlated with CNS metastase could be future radiomic analysis for predicting histopathology and clinical outcome by Chest CT characterization with Artificial Intelligence (AI) Abbreviations CT Computed Tomography MRI Magnetic Resonance Imaging LAD Lung Adenocarcinoma TDR Tumor Disappearance Ratio TIL Tumor Infiltration Lymphocyte WBC White Blood Count KRAS Kirsten rat sarcoma ALK Anaplastic lymphoma kinase GGO Ground Glass Opacity NSCLC Non-Small Cell Lung Cancer DFS Disease Free Survival EGFR Epidermal Growth Factor Receptor CNS Central Nervous System Declarations Ethical Approval Explicit written consent was secured from the patient, as this case report contains no identifiable patient data. This study strictly adheres to ethical principles and has obtained full approval from the Research Ethics Committee of Dr. Soetomo General Hospital, Surabaya. Consent for Publication Written consent for publication had been obtained Funding : None Author Contribution F.A.P and F.H conceived the study. F.A.P developed the theoretical framework and performed the study. F.A.P aided in the analysis. F.H supervised the project. All authors discussed the results and contributed to the final manuscript References Ortiz AFH, Camacho TC, Vásquez AF, del Castillo Herazo V, Neira JGA, Yepes MM, et al. Clinical and CT patterns to predict EGFR mutation in patients with non-small cell lung cancer: A systematic literature review and meta-analysis. Eur J Radiol Open. 2022;9. McLoud T. et. al. Thoracic_Imaging, The_Requisites. Second. Philadelphia: Elsevier; 2019. Wu JJ, Wu CY, Wu CY, Wang CL, Yang TY, Tseng J Sen, et al. Impact of tumor disappearance ratio on the prognosis of lung adenocarcinoma ≤ 2 cm in size: A retrospective cohort study. Journal of the Formosan Medical Association. 2021;120(2):874–82. Ono Y, Tagawa T, Kinoshita F, Haratake N, Takada K, Kohno M, et al. Relationship between consolidation tumor ratio and tumor-infiltrating lymphocytes in small-sized lung adenocarcinoma. Thorac Cancer. 2022;13(15):2134–41. Hattori A, Matsunaga T, Hayashi T, Takamochi K, Oh S, Suzuki K. Prognostic Impact of the Findings on Thin-Section Computed Tomography in Patients with Subcentimeter Non–Small Cell Lung Cancer. In: Journal of Thoracic Oncology. Elsevier Inc; 2017. p. 954–62. Zhong C, Sakurai H, Wei S, Fang W, Asamura H. Sublobar resections for small-sized stage Ia lung adenocarcinoma: A Sino-Japanese multicenter study. J Thorac Dis. 2018;10(2):991–8. Zou Z, Xing P, Hao X, Wang Y, Song X, Shan L, et al. Intracranial efficacy of alectinib in ALK-positive NSCLC patients with CNS metastases—a multicenter retrospective study. BMC Med. 2022;20(1). Wu J, Ding V, Luo S, Choi E, Hellyer J, Myall N, et al. Predictive Model to Guide Brain Magnetic Resonance Imaging Surveillance in Patients With Metastatic Lung Cancer: Impact on Real-World Outcomes. 2022; Available from: https://doi. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7226145","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":494657753,"identity":"d6091986-bf8e-4827-bb4c-31a15d46c2a2","order_by":0,"name":"Firman Adi Prasetyo","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA5klEQVRIiWNgGAWjYBAC9mYg8aHChoeNvfkAkCkhQ1ALz2EGBsYZZ9Lk+HmOJYC08BDWAjSambftsLHkDB8DsABhLey8TzfOOMOcuOEGz+dXN2oseBjYDx/dgFcLM7vZjQ8VbIkbbvdus845BnQYT1raDXxa7JnZ2G7OOMOTuOHO2W3GOWxALRI8Zni18AC13OZtkwA6LOeZcc4/4rUYAL2fw/w4t41ILUCHJYAC2Yw5t0+Ch42QX3j4j7EBvf8fFJWPP+d8q5PjZz98DK8WZMAmASaJVQ4CzB9IUT0KRsEoGAUjBwAAhjlIJy/ILRsAAAAASUVORK5CYII=","orcid":"","institution":"Faculty of Medicine, Airlangga University","correspondingAuthor":true,"prefix":"","firstName":"Firman","middleName":"Adi","lastName":"Prasetyo","suffix":""},{"id":494657754,"identity":"ef8c5763-fd8d-42c2-8d35-fa3071d5cb25","order_by":1,"name":"Fierly Hayati","email":"","orcid":"","institution":"Dr. Soetomo General Academic Hospital","correspondingAuthor":false,"prefix":"","firstName":"Fierly","middleName":"","lastName":"Hayati","suffix":""}],"badges":[],"createdAt":"2025-07-27 12:23:15","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-7226145/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7226145/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":88348658,"identity":"3feb599a-bb6c-4194-bd24-05f7caa8b13c","added_by":"auto","created_at":"2025-08-05 14:01:23","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":122549,"visible":true,"origin":"","legend":"\u003cp\u003eChest xray shows consolidation in right paracardial\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7226145/v1/42dca6510eb930b4e45e7034.png"},{"id":88348663,"identity":"979caeed-c769-4f8d-a909-4fd40a90ec6b","added_by":"auto","created_at":"2025-08-05 14:01:23","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":210197,"visible":true,"origin":"","legend":"\u003cp\u003eContrast Chest CT show solid mass with size +/- 4,1 x 3,1 x 3,5 cm at lateral basal segment of inferior lobe right lung. Solid portion size was 4,037 cm at the mediastinal window setting (B) and total tumor size was measured as 4,494 cm at lung window (A). Thus, TDR was 11% (TDR = Tumor Disappearance Ratio)\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7226145/v1/e555a3a3ed81ee5ea11b7564.png"},{"id":88350295,"identity":"afff2333-7164-4f7f-ad9c-d6f6fbdcb6c0","added_by":"auto","created_at":"2025-08-05 14:09:23","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":122458,"visible":true,"origin":"","legend":"\u003cp\u003eBrain MRI show solid mass in cerebellum which iso intense in T1WI (A) and heterogenous intensity in T2WI (B) and show unrestricted in DWI (C) suggested as brain metastasis\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7226145/v1/505abb43770f3b4836b80d6f.png"},{"id":88350694,"identity":"17c8437f-d1b8-494e-bd98-5c772976cde1","added_by":"auto","created_at":"2025-08-05 14:17:23","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":321457,"visible":true,"origin":"","legend":"\u003cp\u003eAdvanced MR Imaging. (A) MR Perfusion show increase of rCBV and rCBF intra and peri lesion with signal intensity not back to baseline; (B) MR Spectroscopy show increase of Cho/Cr ratio intra and peri lesion\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7226145/v1/7c01eb3aebd3224c4e74f1d4.png"},{"id":88350297,"identity":"77578f58-c6c8-4cdd-9e1c-e2b79cc54cea","added_by":"auto","created_at":"2025-08-05 14:09:23","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":147914,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Chest xray show consolidation in left parahilar. (B) After 10 days, patient has right pleural effusion\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-7226145/v1/e385a2556b68c34bf5c6f9b4.png"},{"id":88348668,"identity":"85b83b0d-2c21-401b-b03c-47244b06fc0a","added_by":"auto","created_at":"2025-08-05 14:01:23","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":187021,"visible":true,"origin":"","legend":"\u003cp\u003eContrast Chest CT show solid mass with size +/- 1,9 x 4,5 x 3,1 cm at the superior segment of lingula superior lobe left lung. Solid portion size was 1,913 cm at the mediastinal window setting (B) and total tumor size was measured as 2,866 cm at lung window (A). Thus, TDR was 33% (TDR = Tumor Disappearance Ratio)\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-7226145/v1/ea6eb1b09481305706fdb3b9.png"},{"id":88350308,"identity":"4fc8e8cf-2881-4e14-aa45-35ac995f8035","added_by":"auto","created_at":"2025-08-05 14:09:24","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":160450,"visible":true,"origin":"","legend":"\u003cp\u003eBrain MRI show multiple solid mass \u0026nbsp;intra axial left parietal region which iso to hyperintens in T1WI and hyperintense in T2WI and show unrestricted in DWI suggested as brain metastases\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-7226145/v1/da5fe13879101ed082320df0.png"},{"id":88348671,"identity":"1732038d-8439-4168-80f2-791d5c41901a","added_by":"auto","created_at":"2025-08-05 14:01:23","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":96143,"visible":true,"origin":"","legend":"\u003cp\u003eChest Xray shows consolidation in right suprahilar\u003c/p\u003e","description":"","filename":"8.png","url":"https://assets-eu.researchsquare.com/files/rs-7226145/v1/805d844aabb512d29f0f117c.png"},{"id":88348673,"identity":"c1271cda-679c-410d-925f-5310c709dafd","added_by":"auto","created_at":"2025-08-05 14:01:23","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":180203,"visible":true,"origin":"","legend":"\u003cp\u003eContrast Chest CT show solid mass with size +/- 1,8 x 2,2 x 1,9 cm at the apical segment of superior lobe right lung. Solid portion size was 1,823 cm at the mediastinal window setting (B) and total tumor size was measured as 2,744 cm at lung window (A). Thus, TDR was 33% (TDR = Tumor Disappearance Ratio)\u003c/p\u003e","description":"","filename":"9.png","url":"https://assets-eu.researchsquare.com/files/rs-7226145/v1/3178737e53846950a848d56b.png"},{"id":88348678,"identity":"44707e0d-e5e7-449b-94da-334995cd31ed","added_by":"auto","created_at":"2025-08-05 14:01:23","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":139715,"visible":true,"origin":"","legend":"\u003cp\u003eBrain MRI show multiple solid mass with cystic component with bigger size 4,1 x 4,2 x 2,4 cm which hypointens in T1WI, iso to hyperintense in T2WI and show partially restricted in DWI with bone defect at right parietal\u003c/p\u003e","description":"","filename":"10.png","url":"https://assets-eu.researchsquare.com/files/rs-7226145/v1/93898dbce4e1f65e7da67a0d.png"},{"id":88348675,"identity":"068205ef-8838-40ba-8b3b-0de35ffc42bf","added_by":"auto","created_at":"2025-08-05 14:01:23","extension":"png","order_by":11,"title":"Figure 11","display":"","copyAsset":false,"role":"figure","size":535813,"visible":true,"origin":"","legend":"\u003cp\u003eImmuno Histo Chemistry (IHC) examination show positive for TTF-1 (A) CK 7 (B) Napsin (C) and negative for thyroglobulin (D) with conclusion as Matastatic adenocarcinoma from Lung\u003c/p\u003e","description":"","filename":"11.png","url":"https://assets-eu.researchsquare.com/files/rs-7226145/v1/e96967c924fe33c0c0583283.png"},{"id":88352417,"identity":"3628cf5f-3c3d-4a18-9281-100184837383","added_by":"auto","created_at":"2025-08-05 14:33:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2941947,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7226145/v1/0e35ff61-4814-4ae9-8623-58e3f4f9450c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical Significance of Tumor Disappearance Ratio in EGFR-Mutant Lung Adenocarcinoma with Brain Metastases: A Case Series","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eRepresenting 18% of all cancer cases, lung cancer is among the most frequent non-hematologic malignancies, predominantly affecting males with a median age of 70. Lung adenocarcinoma (LAD) stands as the most common histological subtype in non-small cell lung cancer (NSCLC), influenced by genetic mutations in EGFR, KRAS, and ALK. Adenocarcinoma now accounts for about half of all lung cancer diagnoses, being especially prevalent in females and non-smokers. Usually arising in the lung periphery, these tumors are often asymptomatic. Despite their slow growth pattern, adenocarcinomas are known for early metastatic potential. Radiographically, they appear as solitary nodules or masses with irregular margins such as spiculated or lobulated edges. CT imaging commonly reveals ground-glass opacities around the tumor, and in about 20% of cases, a pneumonia-like consolidation may also be present, occasionally accompanied by nodules in other lobes. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eLAD characterized by ground-glass opacities (GGO) typically demonstrates a favorable prognosis, with pathology frequently revealing limited invasion. The tumor disappearance ratio (TDR) has gained recognition as a prognostic parameter. In tumors measuring 2 cm or less, a low TDR correlates with greater pathological invasiveness, including pleural and lymphovascular invasion, as well as more advanced pathological stages. Moreover, individuals with lower TDR tend to experience shorter recurrence-free and overall survival durations. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eTumor infiltration lymphocytes (TILs) play a pivotal role in the body\u0026rsquo;s immune defense against malignancies. In GGO-pattern LAD, tumors with high consolidation were found to contain more TILs than those with lower consolidation. LADs that lack solid components pathologically identified as adenocarcinoma in situ (AIS) exhibit reduced immune activity against tumor cells. In advanced LAD, EGFR wild-type tumors had increased CD8\u0026thinsp;+\u0026thinsp;TIL infiltration and greater PD-L1 expression compared to tumors with EGFR mutations. The importance of detecting EGFR mutations in LAD has grown in recent years due to the superior clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) over standard chemotherapy in appropriately selected cases (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eThere is variation in the reported cut-off values for the solid component ratio in lung tumors. Wu et al. identified a TDR of \u0026le;\u0026thinsp;75% as an independent risk factor associated with reduced 5-year disease-free survival (DFS) and a trend toward unfavorable overall survival (OS) after resection. Prior literature has also emphasized that the proportion of solid parts or GGO features may serve as important indicators of prognosis, with relevant concepts including the consolidation-to-tumor ratio (CTR), GGO ratio, and TDR. Hattori et al. demonstrated that patients with tumors\u0026thinsp;\u0026le;\u0026thinsp;1 cm exhibiting GGO on CT had improved DFS. Similarly, the Japan Clinical Oncology Group 0201 (JCOG 0201) found that adenocarcinomas measuring\u0026thinsp;\u0026le;\u0026thinsp;2 cm with a CTR\u0026thinsp;\u0026le;\u0026thinsp;25% were associated with minimally invasive pathological profiles. Other research supports a 50% threshold for either the CTR or the GGO ratio. (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e"},{"header":"CASE PRESENTATION","content":"\u003cp\u003eWe reported three cases of Lung Adenocarcinoma EGFR mutation with TDR\u0026thinsp;\u0026lt;\u0026thinsp;75% and CNS Metastase. All of the patient\u0026rsquo;s first CXR only show consolidation but Chest CT and Histopathology confirm with Lung Adenocarcinoma EGFR mutation. All of those patients had neurology complaint as first symptoms rather than respiratory symptoms.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eCase 1\u003c/strong\u003e\u003cp\u003eFemale 69 years old non-smoker with Headache. The patient complained of chronic headache. There is no fever, no cough, no dyspnea. Then the patient performed brain MRI result show the cerebellar metastatic process (Figs.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). After that, the patient underwent chest xray that only show consolidation in right paracardial (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) but chest ct show lung mass (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) followed by histopathology examination result as lung adenocarcinoma with EGFR mutation. Then the patient has lower respiratory tract infection and sepsis with WBC 14.710 and Procalcitonin 7,76 ng/ml. Patient died because of sepsis after 7 days of treatment.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eCase 2\u003c/strong\u003e\u003cp\u003eMale 49 years old non-smoker with right hemianesthesia. The patient complain with numbness and tingling of his right limb, there is no headache, no dyspnea, no chough nor seizure. Then patient performed brain MRI and show as brain metastase (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e). After that, the patient underwent chest xray that only show consolidation in left parahilar (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e) but chest ct (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e) show lung mass followed by histopathology examination result as lung adenocarcinoma with EGFR mutation. Then patient underwent for chemotherapy. After 10 days, patient has dyspnea and chest xray show right pleural effusion. Then patient had thoracocentesis but respiratory failure still exist and patient dead.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eCase 3\u003c/strong\u003e\u003cp\u003eMale 48 years old non-smoker with seizure. The patient had seizure, whole body spasm and eyes glancing upwards. First, patient was diagnosed as meningioma and performed brain surgery. The histopathology result show that metastatic adenocarcinoma from lung (Fig.\u0026nbsp;\u003cspan refid=\"Fig11\" class=\"InternalRef\"\u003e11\u003c/span\u003e). Then patient underwent chest xray with consolidation at right suprahilar (Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e) followed by histopathology examination result as lung adenocarcinoma with EGFR mutation. Then patient underwent chemotherapy and radiotherapy, the patient had success for the ct evaluation as partial response.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSummarize TDR Cases\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCase\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eClinical Information\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eTDR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eStaging\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eEGFR mutation\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eCNS Metastaes\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCase \u003cspan refid=\"FPar1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFemale 69 years old with chronic headache\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSt IVb\u003c/p\u003e\u003cp\u003e(T2N3M1c)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eExon 20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eCerebellar\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCase \u003cspan refid=\"FPar2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale 49 years old with right hemianesthesia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSt IVb\u003c/p\u003e\u003cp\u003e(T2N3M1c)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eExon 19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eCerebral\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCase \u003cspan refid=\"FPar3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale 48 years old with seizure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSt IVa (T1cN1M1b)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eExon 18,19,20,21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eCerebral\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eLung Adenocarcinoma with EGFR mutation are strong correlation with Brain metastase. These three cases (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) have Brain metastase which two cases manifest as cerebral metastase and one case manifest as cerebellar metastase. Histology and disease stage of the initial lung cancer are among the major determinants of brain metastasis formation. Furthermore, the position of the primary tumor plays a role, as centrally located lesions appear more likely to metastasize to the brain. This statement only suitable with one case that location in central perihilar, but the others location are in peripheral. (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eOrtiz AFH et al. (2022) conducted an investigation involving 10,355 NSCLC patients to identify CT and clinical markers linked with EGFR mutation status. Their analysis revealed that GGO, air bronchogram, vascular convergence, pleural retraction, non-smoking status, and being female were independently associated with a higher likelihood of EGFR mutations in lung adenocarcinoma. This conclusion is supported by three cases presenting these radiological features alongside non-smoking history; however, two of the patients were male (aged 40\u0026ndash;50) and one was a 69-year-old female. Supporting meta-analyses have similarly reported that air bronchogram, spiculated edges, and GGO are dominant CT characteristics frequently observed in EGFR-mutated adenocarcinomas.\u003c/p\u003e\u003cp\u003eWu et. al (2021) analyzed pre-surgical focused on clinical lymph node and distant metastatic status. None of the patients with a TDR\u0026thinsp;\u0026gt;\u0026thinsp;75% demonstrated nodal or distant spread. In contrast, 31.0% of patients with TDR\u0026thinsp;\u0026le;\u0026thinsp;75% presented with either lymph node involvement or distant metastasis, and 27.6% had distant metastasis specifically. Tumor cells can infiltrate blood or lymphatic vessels, travel through circulation, and colonize new sites. Remarkably, the angiogenic switch may be activated even in tumors under 1 cm in size. Pathologically, most TDR\u0026thinsp;\u0026le;\u0026thinsp;75% cases on chest CT revealed micropapillary or solid components, which correlated with increased invasiveness in the solid portions visible on imaging.\u003c/p\u003e\u003cp\u003eTumor Disappearance Ratio (TDR) of the three cases are below 75% which is suitable with previous studies that low TDR correlated to more pathological invasiveness such as pleural invasion, lymphovascular invasion, and advanced pathological staging. Two cases have TDR of 33% (Figs.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e and \u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e9\u003c/span\u003e ) and one cases has TDR of 11% (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). All of these cases have advanced pathological staging with CNS metastases. One case has progressive pleural invasion as pleural effusion.\u003c/p\u003e\u003cp\u003eCNS metastases continue to pose a major threat to patients with advanced NSCLC, significantly impairing neurological function, cognitive performance, and survival outcomes. It is estimated that approximately 30\u0026ndash;40% of patients with advanced NSCLC develop metastasis to the central nervous system. The presence of specific tumor genomic alterations, particularly EGFR or ALK driver mutations, has been associated with a greater likelihood of brain metastases in these patients. (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e)\u003c/p\u003e\u003cp\u003eIt has been reported that exon 21 EGFR mutations are more commonly associated with tumors exhibiting a greater extent of GGO, while exon 19 mutations are typically found in tumors that are smaller in size and demonstrate pleural retraction. Two cases have a mutation in exon 21 but no difference in GGO with the same TDR 33% in one case mutation in exon 19. Two cases have a mutation in exon 19 which is suitable with the meta-analysis result by presence of pleural retraction. The meta-analysis studies also state that individuals from Asia have an increase prevalence of EGFR mutation in NSCLC.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eLow TDR value correlate with vascular invasion that presence as CNS Metastase in Lung Adenocarcinoma with EGFR mutation. The most frequent CT patterns associated with lung adenocarcinoma EGFR mutation are air bronchogram, spiculated margins and GGO. The characterization in LAD with EGFR mutation correlated with CNS metastase could be future radiomic analysis for predicting histopathology and clinical outcome by Chest CT characterization with Artificial Intelligence (AI)\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCT\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eComputed Tomography\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMRI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMagnetic Resonance Imaging\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eLAD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eLung Adenocarcinoma\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTDR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eTumor Disappearance Ratio\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTIL\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eTumor Infiltration Lymphocyte\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eWBC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eWhite Blood Count\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eKRAS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eKirsten rat sarcoma\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eALK\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAnaplastic lymphoma kinase\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eGGO\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eGround Glass Opacity\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eNSCLC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eNon-Small Cell Lung Cancer\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eDFS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eDisease Free Survival\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eEGFR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eEpidermal Growth Factor Receptor\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCNS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eCentral Nervous System\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eExplicit written consent was secured from the patient, as this case report contains no identifiable patient data. This study strictly adheres to ethical principles and has obtained full approval from the Research Ethics Committee of Dr. Soetomo General Hospital, Surabaya.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten consent for publication had been obtained\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eF.A.P and F.H conceived the study. F.A.P developed the theoretical framework and performed the study. F.A.P aided in the analysis. F.H supervised the project. All authors discussed the results and contributed to the final manuscript\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eOrtiz AFH, Camacho TC, V\u0026aacute;squez AF, del Castillo Herazo V, Neira JGA, Yepes MM, et al. Clinical and CT patterns to predict EGFR mutation in patients with non-small cell lung cancer: A systematic literature review and meta-analysis. Eur J Radiol Open. 2022;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMcLoud T. et. al. Thoracic_Imaging, The_Requisites. Second. Philadelphia: Elsevier; 2019.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWu JJ, Wu CY, Wu CY, Wang CL, Yang TY, Tseng J Sen, et al. Impact of tumor disappearance ratio on the prognosis of lung adenocarcinoma\u0026thinsp;\u0026le;\u0026thinsp;2 cm in size: A retrospective cohort study. Journal of the Formosan Medical Association. 2021;120(2):874\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOno Y, Tagawa T, Kinoshita F, Haratake N, Takada K, Kohno M, et al. Relationship between consolidation tumor ratio and tumor-infiltrating lymphocytes in small-sized lung adenocarcinoma. Thorac Cancer. 2022;13(15):2134\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHattori A, Matsunaga T, Hayashi T, Takamochi K, Oh S, Suzuki K. Prognostic Impact of the Findings on Thin-Section Computed Tomography in Patients with Subcentimeter Non\u0026ndash;Small Cell Lung Cancer. In: Journal of Thoracic Oncology. Elsevier Inc; 2017. p. 954\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhong C, Sakurai H, Wei S, Fang W, Asamura H. Sublobar resections for small-sized stage Ia lung adenocarcinoma: A Sino-Japanese multicenter study. J Thorac Dis. 2018;10(2):991\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZou Z, Xing P, Hao X, Wang Y, Song X, Shan L, et al. Intracranial efficacy of alectinib in ALK-positive NSCLC patients with CNS metastases\u0026mdash;a multicenter retrospective study. BMC Med. 2022;20(1).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWu J, Ding V, Luo S, Choi E, Hellyer J, Myall N, et al. Predictive Model to Guide Brain Magnetic Resonance Imaging Surveillance in Patients With Metastatic Lung Cancer: Impact on Real-World Outcomes. 2022; Available from: https://doi.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Tumor Disappearance Ratio, Lung Adenocarcinoma, EGFR Mutation, CNS Metastases","lastPublishedDoi":"10.21203/rs.3.rs-7226145/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7226145/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eAmong lung cancer subtypes, lung adenocarcinoma is the most frequently diagnosed histologic form and is commonly impacted by EGFR mutations. Tumor disappearance ratio (TDR) has been proposed as a prognostic marker. A decreased TDR tends to be linked with more invasive pathological characteristics, including pleural and lymphovascular involvement and advanced tumor stage. Notably, chest CT findings in patients with TDR\u0026thinsp;\u0026le;\u0026thinsp;75% often revealed micropapillary or solid patterns that corresponded with higher invasiveness.\u003c/p\u003e\u003ch2\u003eCase presentation:\u003c/h2\u003e\u003cp\u003eWe reported three cases of Lung Adenocarcinoma with TDR\u0026thinsp;\u0026lt;\u0026thinsp;75% and CNS Metastases. All of the patient\u0026rsquo;s first CXR only shows consolidation but Chest CT and Histopathology confirm with Lung Adenocarcinoma EGFR mutation. All of those patients had neurology complaints as first symptoms rather than respiratory symptoms. First, Female 69 years old complained of chronic headache, then the patient performed brain MRI results show the cerebellar metastatic process. After that, the patient underwent chest CT show lung mass with TDR 11%. Then the patient has lower respiratory tract infection and sepsis with WBC 14.710 and procalcitonin 7,76 ng/ml. The patient died because of sepsis after 7 days of treatment. Second, Male 49 years old with right hemianesthesia. The patient complained of numbness and tingling of his right limb, the patient performed a brain MRI and show as brain metastasis. After that, the patient underwent chest CT show lung mass with TDR 33%. Then patient underwent for chemotherapy. After 10 days, patient has dyspnea and CXR show right pleural effusion. Then patient had thoracocentesis but respiratory failure still existed and patient died. Last case, Male 48 years old with a seizure, whole body spasm and eyes glancing upwards. First, patient was diagnosed as meningioma and performed brain surgery. The histopathology result show that metastatic adenocarcinoma from the lung. The patient underwent chest CT show lung mass with TDR 33%. Then patient underwent chemotherapy and radiotherapy, the patient had success for the CT evaluation as a partial response.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eLow TDR value correlate with a vascular invasion that present as Brain Metastases in Lung Adenocarcinoma with EGFR mutation.\u003c/p\u003e","manuscriptTitle":"Clinical Significance of Tumor Disappearance Ratio in EGFR-Mutant Lung Adenocarcinoma with Brain Metastases: A Case Series","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-05 14:01:18","doi":"10.21203/rs.3.rs-7226145/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"cfe147ac-4f1d-48a6-a959-172ab91d5cff","owner":[],"postedDate":"August 5th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-05T14:01:20+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-05 14:01:18","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7226145","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7226145","identity":"rs-7226145","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}