Faculty Profiles - NAGANAWA, Shinji

Diffusion Tensor Image Analysis ALong the Perivascular Space (DTI-ALPS): Revisiting the Meaning and Significance of the Method. Reviewed

Toshiaki Taoka, Rintaro Ito, Rei Nakamichi, Toshiki Nakane, Hisashi Kawai, Shinji Naganawa

Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine Vol. 23 ( 3 ) page： 268 - 290 2024

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

More than 5 years have passed since the Diffusion Tensor Image Analysis ALong the Perivascular Space (DTI-ALPS) method was proposed with the intention of evaluating the glymphatic system. This method is handy due to its noninvasiveness, provision of a simple index in a straightforward formula, and the possibility of retrospective analysis. Therefore, the ALPS method was adopted to evaluate the glymphatic system for many disorders in many studies. The purpose of this review is to look back and discuss the ALPS method at this moment.The ALPS-index was found to be an indicator of a number of conditions related to the glymphatic system. Thus, although this was expected in the original report, the results of the ALPS method are often interpreted as uniquely corresponding to the function of the glymphatic system. However, a number of subsequent studies have pointed out the problems on the data interpretation. As they rightly point out, a higher ALPS-index indicates predominant Brownian motion of water molecules in the radial direction at the lateral ventricular body level, no more and no less. Fortunately, the term "ALPS-index" has become common and is now known as a common term by many researchers. Therefore, the ALPS-index should simply be expressed as high or low, and whether it reflects a glymphatic system is better to be discussed carefully. In other words, when a decreased ALPS-index is observed, it should be expressed as "decreased ALPS-index" and not directly as "glymphatic dysfunction". Recently, various methods have been proposed to evaluate the glymphatic system. It has become clear that these methods also do not seem to reflect the entirety of the extremely complex glymphatic system. This means that it would be desirable to use various methods in combination to evaluate the glymphatic system in a comprehensive manner.

DOI： 10.2463/mrms.rev.2023-0175

Association between the Putative Meningeal Lymphatics at the Posterior Wall of the Sigmoid Sinus and Delayed Contrast-agent Elimination from the Cerebrospinal Fluid. Reviewed

Shinji Naganawa, Rintaro Ito, Mariko Kawamura, Toshiaki Taoka, Tadao Yoshida, Michihiko Sone

Magnetic resonance in medical sciences : MRMS : an official journal of Japan Society of Magnetic Resonance in Medicine Vol. 23 ( 1 ) page： 80 - 91 2024

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: To investigate the characteristics of the putative meningeal lymphatics located at the posterior wall of the sigmoid sinus (PML-PSS) in human subjects imaged before and after intravenous administration (IV) of a gadolinium-based contrast agent (GBCA). The appearance of the PML-PSS and the enhancement of the perivascular space of the basal ganglia (PVS-BG) were analyzed for an association with gender, age, and clearance of the GBCA from the cerebrospinal fluid (CSF). METHODS: Forty-two patients with suspected endolymphatic hydrops were included. Heavily T2-weighted 3D-fluid attenuated inversion recovery (hT2w-3D-FLAIR) and 3D-real inversion recovery (IR) images were obtained at pre-administration, immediately post-administration, and at 4 and 24 hours after IV-GBCA. The appearance of the PML-PSS and the presence of enhancement in the PVS-BG were analyzed for a relationship with age, gender, contrast enhancement of the CSF at 4 hours after IV-GBCA, and the washout ratio of the GBCA in the CSF from 4 to 24 hours after IV-GBCA. RESULTS: The PML-PSS and PVS-BG were seen in 23 of 42 and 21 of 42 cases, respectively, at 4 hours after IV-GBCA. In all PML-PSS positive cases, hT2w-3D-FLAIR signal enhancement was highest at 4 hours after IV-GBCA. A multivariate analysis between gender, age, CSF signal elevation at 4 hours, and washout ratio indicated that only the washout ratio was independently associated with the enhancement of the PML-PSS or PVS-BG. The odds ratios (95% CIs; P value) were 4.09 × 10-5 (2.39 × 10-8 - 0.07; 0.0078) for the PML-PSS and 1.7 × 10-4 (1.66 × 10-7 - 0.174; 0.014) for the PVS-BG. CONCLUSION: The PML-PSS had the highest signal enhancement at 4 hours after IV-GBCA. When the PML-PSS was seen, there was also often enhancement of the PVS-BG at 4 hours after IV-GBCA. Both observed enhancements were associated with delayed GBCA excretion from the CSF.

DOI： 10.2463/mrms.mp.2022-0110

Assessing the Real-World, Long-Term Impact of Lemborexant on Sleep Quality in a Home-Based Clinical Study. Reviewed International journal

Seiko Miyata, Kunihiro Iwamoto, Ippei Okada, Akihiro Fujimoto, Yuki Kogo, Daisuke Mori, Manabu Amano, Nao Matsuyama, Kazuki Nishida, Masahiko Ando, Toshiaki Taoka, Shinji Naganawa, Norio Ozaki

Nature and science of sleep Vol. 16 page： 291 - 303 2024

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Both subjective and objective evaluations are essential for the treatment of insomnia. Lemborexant has been shown to be effective in the long-term based solely on a subjective basis, and no long-term objective measures have been evaluated under natural sleep conditions. Small, lightweight sleep electroencephalogram (EEG) monitor was used, instead of polysomnography, to objectively evaluate sleep at home 4 and 12 weeks after lemborexant treatment. PATIENTS AND METHODS: Adults and elderly subjects with insomnia disorder, per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, were enrolled in this open-label, single-arm, single-center trial. Objective and subjective measures of sleep were prospectively assessed. Sleep disturbance, excessive sleepiness, and depressive symptoms were assessed using questionnaires. RESULTS: A total of 45 subjects were screened, of which 33 were enrolled. Paired t-tests were conducted to evaluate changes in sleep variables and compared with the baseline; subjects showed significant improvements in objective sleep efficiency (SE) and subjective sleep parameters at weeks 4 and 12 following treatment with lemborexant. When baseline values were taken into account, a repeated-multivariate analysis of variance (MANOVA) revealed statistically significant changes in the objective measures. Sleep disturbance, excessive sleepiness, and depressive symptoms improved after three months of lemborexant treatment. CONCLUSION: Furthermore, lemborexant therapy improved nocturnal sleep, when measured objectively using sleep EEG monitoring at home, and improved daytime sleepiness and depressive symptoms in older adults with insomnia disorder.

DOI： 10.2147/NSS.S448871

Measurement of solid size in early-stage lung adenocarcinoma by virtual 3D thin-section CT applied artificial intelligence. Reviewed International journal Open Access

Shingo Iwano, Shinichiro Kamiya, Rintaro Ito, Akira Kudo, Yoshiro Kitamura, Keigo Nakamura, Shinji Naganawa

Scientific reports Vol. 13 ( 1 ) page： 21709 - 21709 2023.12

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

An artificial intelligence (AI) system that reconstructs virtual 3D thin-section CT (TSCT) images from conventional CT images by applying deep learning was developed. The aim of this study was to investigate whether virtual and real TSCT could measure the solid size of early-stage lung adenocarcinoma. The pair of original thin-CT and simulated thick-CT from the training data with TSCT images (thickness, 0.5-1.0 mm) of 2700 pulmonary nodules were used to train the thin-CT generator in the generative adversarial network (GAN) framework and develop a virtual TSCT AI system. For validation, CT images of 93 stage 0-I lung adenocarcinomas were collected, and virtual TSCTs were reconstructed from conventional 5-mm thick-CT images using the AI system. Two radiologists measured and compared the solid size of tumors on conventional CT and virtual and real TSCT. The agreement between the two observers showed an almost perfect agreement on the virtual TSCT for solid size measurements (intraclass correlation coefficient = 0.967, P < 0.001, respectively). The virtual TSCT had a significantly stronger correlation than that of conventional CT (P = 0.003 and P = 0.001, respectively). The degree of agreement between the clinical T stage determined by virtual TSCT and the clinical T stage determined by real TSCT was excellent in both observers (k = 0.882 and k = 0.881, respectively). The AI system developed in this study was able to measure the solid size of early-stage lung adenocarcinoma on virtual TSCT as well as on real TSCT.

DOI： 10.1038/s41598-023-48755-5

Recent advances in artificial intelligence for cardiac CT: Enhancing diagnosis and prognosis prediction Reviewed

Disruption of the Blood-Perilymph Barrier Preceding Endolymphatic Hydrops Formation in Meniere's Disease Reviewed Open Access

Masumi Kobayashi, Tadao Yoshida, Satofumi Sugimoto, Shinji Naganawa, Michihiko Sone

OTOLOGY & NEUROTOLOGY Vol. 44 ( 10 ) page： E766 - E767 2023.12

第1章　画像診断機器　【基調論文】最新医療機器の現況と将来的方向性 2024年　最新医療機器の現状と展望 CTやMRIなどの画像診断装置の技術的到達点への評価と課題 Reviewed

長縄慎二

月間新医療データブック・シリーズ　医療機器システム白書 2024 page： 8 - 11 2023.12

公益社団法人愛知県医師会「現代医学」誌70巻号の特集テーマ「がん検診」座談会 Invited Reviewed

長縄慎二

現代醫学 Vol. 70 ( 2 ) page： 1 - 13 2023.12

Fuminari Tatsugami, Takeshi Nakaura, Masahiro Yanagawa, Shohei Fujita, Koji Kamagata, Rintaro Ito, Mariko Kawamura, Yasutaka Fushimi, Daiju Ueda, Yusuke Matsui, Akira Yamada, Noriyuki Fujima, Tomoyuki Fujioka, Taiki Nozaki, Takahiro Tsuboyama, Kenji Hirata, Shinji Naganawa

Diagnostic and Interventional Imaging Vol. 104 ( 11 ) page： 521 - 528 2023.11

＜Editors' Choice＞ Pattern of THK 5351 retention in normal aging involves core regions of resting state networks associated with higher cognitive function. Reviewed Open Access

Yusuke Yoshida, Takamasa Yokoi, Kazuhiro Hara, Hirohisa Watanabe, Hiroshi Yamaguchi, Epifanio Bagarinao, Michihito Masuda, Toshiyasu Kato, Aya Ogura, Reiko Ohdake, Kazuya Kawabata, Masahisa Katsuno, Katsuhiko Kato, Shinji Naganawa, Nobuyuki Okamura, Kazuhiko Yanai, Gen Sobue

Nagoya journal of medical science Vol. 85 ( 4 ) page： 758 - 771 2023.11

Language：English Publishing type：Research paper (scientific journal)

We aimed to elucidate the distribution pattern of the positron emission tomography probe [18F]THK 5351, a marker for astrogliosis and tau accumulation, in healthy aging. We also assessed the relationship between THK5351 retention and resting state networks. We enrolled 62 healthy participants in this study. All participants underwent magnetic resonance imaging/positron emission tomography scanning consisting of T1-weighted images, resting state functional magnetic resonance imaging, Pittsburgh Compound-B and THK positron emission tomography. The preprocessed THK images were entered into a scaled subprofile modeling/principal component analysis to extract THK distribution patterns. Using the most significant THK pattern, we generated regions of interest, and performed seed-based functional connectivity analyses. We also evaluated the functional connectivity overlap ratio to identify regions with high between-network connectivity. The most significant THK distributions were observed in the medial prefrontal cortex and bilateral putamen. The seed regions of interest in the medial prefrontal cortex had a functional connectivity map that significantly overlapped with regions of the dorsal default mode network. The seed regions of interest in the putamen showed strong overlap with the basal ganglia and anterior salience networks. The functional connectivity overlap ratio also showed that three peak regions had the characteristics of connector hubs. We have identified an age-related spatial distribution of THK in the medial prefrontal cortex and basal ganglia in normal aging. Interestingly, the distribution's peaks are located in regions of connector hubs that are strongly connected to large-scale resting state networks associated with higher cognitive function.

DOI： 10.18999/nagjms.85.4.758

From FDG and beyond: the evolving potential of nuclear medicine. Reviewed

Kenji Hirata, Koji Kamagata, Daiju Ueda, Masahiro Yanagawa, Mariko Kawamura, Takeshi Nakaura, Rintaro Ito, Fuminari Tatsugami, Yusuke Matsui, Akira Yamada, Yasutaka Fushimi, Taiki Nozaki, Shohei Fujita, Tomoyuki Fujioka, Takahiro Tsuboyama, Noriyuki Fujima, Shinji Naganawa

Annals of nuclear medicine Vol. 37 ( 11 ) page： 583 - 595 2023.11

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

The radiopharmaceutical 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) has been dominantly used in positron emission tomography (PET) scans for over 20 years, and due to its vast utility its applications have expanded and are continuing to expand into oncology, neurology, cardiology, and infectious/inflammatory diseases. More recently, the addition of artificial intelligence (AI) has enhanced nuclear medicine diagnosis and imaging with FDG-PET, and new radiopharmaceuticals such as prostate-specific membrane antigen (PSMA) and fibroblast activation protein inhibitor (FAPI) have emerged. Nuclear medicine therapy using agents such as [177Lu]-dotatate surpasses conventional treatments in terms of efficacy and side effects. This article reviews recently established evidence of FDG and non-FDG drugs and anticipates the future trajectory of nuclear medicine.

DOI： 10.1007/s12149-023-01865-6

Diffusivity Along the Perivascular Space is Decreased and Related to Hypoperfusion in Adult Moyamoya disease Reviewed

Shoko Hara, Junko Kikuta, Kaito Takabayashi, Koji Kamagata, Shihori Hayashi, Motoki Inaji, Yoji Tanaka, Masaaki Hori, Kenji Ishii, Tadashi Nariai, Toshiaki Taoka, Shinji Naganawa, Shigeki Aoki, Taketoshi Maehara

in press (https://www.researchsquare.com/article/rs-3411760/v1) 2023.10

New trend in artificial intelligence-based assistive technology for thoracic imaging. Reviewed International journal Open Access

Masahiro Yanagawa, Rintaro Ito, Taiki Nozaki, Tomoyuki Fujioka, Akira Yamada, Shohei Fujita, Koji Kamagata, Yasutaka Fushimi, Takahiro Tsuboyama, Yusuke Matsui, Fuminari Tatsugami, Mariko Kawamura, Daiju Ueda, Noriyuki Fujima, Takeshi Nakaura, Kenji Hirata, Shinji Naganawa

La Radiologia medica Vol. 128 ( 10 ) page： 1236 - 1249 2023.10

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

Although there is no solid agreement for artificial intelligence (AI), it refers to a computer system with intelligence similar to that of humans. Deep learning appeared in 2006, and more than 10 years have passed since the third AI boom was triggered by improvements in computing power, algorithm development, and the use of big data. In recent years, the application and development of AI technology in the medical field have intensified internationally. There is no doubt that AI will be used in clinical practice to assist in diagnostic imaging in the future. In qualitative diagnosis, it is desirable to develop an explainable AI that at least represents the basis of the diagnostic process. However, it must be kept in mind that AI is a physician-assistant system, and the final decision should be made by the physician while understanding the limitations of AI. The aim of this article is to review the application of AI technology in diagnostic imaging from PubMed database while particularly focusing on diagnostic imaging in thorax such as lesion detection and qualitative diagnosis in order to help radiologists and clinicians to become more familiar with AI in thorax.

DOI： 10.1007/s11547-023-01691-w

Multisite harmonization of diffusion tensor image analysis along the perivascular space using the COMBined Association Test. Reviewed Open Access

Yuya Saito, Koji Kamagata, Christina Andica, Toshiaki Taoka, Rukeye Tuerxun, Wataru Uchida, Kaito Takabayashi, Mana Owaki, Seina Yoshida, Keigo Yamazaki, Shinji Naganawa, Shigeki Aoki

Japanese journal of radiology Vol. 41 ( 10 ) page： 1072 - 1083 2023.10

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: This multisite study aimed to use the COMBined Association Test (COMBAT), a harmonization technique that uses regression of covariates with an empirical Bayesian framework, to harmonize diffusion tensor image analysis along the perivascular space (DTI-ALPS) variations caused by scanner, site, and protocol differences. MATERIALS AND METHODS: This study included multisite diffusion magnetic resonance imaging (dMRI) data of 45 patients with Alzheimer's disease (AD) and 82 cognitively normal (CN) participants from the AD neuroimaging initiative database. The dMRI data were obtained with two b values (0 and 1000 s/mm2) from 27 institutions and three different 3-Tesla MRI scanners (two vendors). The ALPS index was calculated from multisite dMRI data, and COMBAT was used to harmonize the factors causing site variations. Welch's t test was used, Cohen's d was calculated to compare the difference in the ALPS index between AD and CN before and after harmonization, and Pearson's correlation coefficient was calculated to assess the relationships between the ALPS index and the cognitive score, [18F] fluorodeoxyglucose (FDG)-positron emission tomography (PET), and [18F] florbetapir (AV45)-PET standardized uptake value ratios (SUVRs). RESULTS: COMBAT harmonized scanner differences and increased Cohen's d of the left and right ALPS indexes between AD and CN from 0.288 to 0.438 and 0.328 to 0.480, respectively. The ALPS indexes were significantly different between AD and CN after harmonization (P < 0.05) but not before it. Moreover, Pearson's correlation coefficients between the ALPS index and cognitive score, FDG-PET, and AV45-PET SUVRs were higher after harmonization than before it. CONCLUSION: This study demonstrates the application of COMBAT harmonization to eliminate between-scanner, site, and protocol variations in the ALPS index calculated from DTI-ALPS using dMRI and possibly facilitate the use of the ALPS index in multi-center studies.

DOI： 10.1007/s11604-023-01432-z

MOGADのGlymphatic systemのDTI-ALPSを用いた解析 Reviewed

宮地真由, 富沢雄二, 星野泰延, コッス・ダビデ, 萩原彰文, 鎌形康司, 関根永久, 高林海斗, 田岡俊昭, 仲谷元, 横山和正, 長縄慎二, 青木茂樹, 服部信孝

臨床神経学 Vol. 63 ( Suppl. ) page： S275 - S275 2023.9

A Brain Morphometry Study with Across-Site Harmonization Using a ComBat-Generalized Additive Model in Children and Adolescents. Reviewed International journal Open Access

Tadashi Shiohama, Norihide Maikusa, Masahiro Kawaguchi, Jun Natsume, Yoshiyuki Hirano, Keito Saito, Jun-Ichi Takanashi, Jacob Levman, Emi Takahashi, Koji Matsumoto, Hajime Yokota, Shinya Hattori, Keita Tsujimura, Daisuke Sawada, Tomoko Uchida, Tomozumi Takatani, Katsunori Fujii, Shinji Naganawa, Noriko Sato, Hiromichi Hamada

Diagnostics (Basel, Switzerland) Vol. 13 ( 17 ) 2023.9

Language：English Publishing type：Research paper (scientific journal)

Regional anatomical structures of the brain are intimately connected to functions corresponding to specific regions and the temporospatial pattern of genetic expression and their functions from the fetal period to old age. Therefore, quantitative brain morphometry has often been employed in neuroscience investigations, while controlling for the scanner effect of the scanner is a critical issue for ensuring accuracy in brain morphometric studies of rare orphan diseases due to the lack of normal reference values available for multicenter studies. This study aimed to provide across-site normal reference values of global and regional brain volumes for each sex and age group in children and adolescents. We collected magnetic resonance imaging (MRI) examinations of 846 neurotypical participants aged 6.0-17.9 years (339 male and 507 female participants) from 5 institutions comprising healthy volunteers or neurotypical patients without neurological disorders, neuropsychological disorders, or epilepsy. Regional-based analysis using the CIVET 2.1.0. pipeline provided regional brain volumes, and the measurements were across-site combined using ComBat-GAM harmonization. The normal reference values of global and regional brain volumes and lateral indices in our study could be helpful for evaluating the characteristics of the brain morphology of each individual in a clinical setting and investigating the brain morphology of ultra-rare diseases.

DOI： 10.3390/diagnostics13172774

Four-dimensional Flow MRI Assessment of Portal Hemodynamics and Hepatic Regeneration after Portal Vein Embolization. Reviewed International journal Open Access

Ryota Hyodo, Yasuo Takehara, Takashi Mizuno, Kazushige Ichikawa, Ryota Horiguchi, Shoji Kawakatsu, Takashi Mizuno, Tomoki Ebata, Shinji Naganawa, Ning Jin, Yoshito Ichiba

Radiology Vol. 308 ( 3 ) page： e230709 2023.9

Language：English Publishing type：Research paper (scientific journal)

Background Percutaneous transhepatic portal vein (PV) embolization (PVE) is a standard preoperative procedure for advanced biliary cancer when the future liver remnant (FLR) is insufficient, yet the effect of this procedure on portal hemodynamics is still unclear. Purpose To assess whether four-dimensional (4D) MRI flowmetry can be used to estimate FLR volume and to identify the optimal time for this measurement. Materials and Methods This prospective single-center study enrolled consecutive adult patients with biliary cancer who underwent percutaneous transhepatic PVE for the right liver between June 2020 and November 2022. Portal hemodynamics were assessed using 4D flow MRI before PVE and within 1 day (0-day group) or 3-4 days (3-day group) after PVE. FLR volume was measured using CT before PVE and after PVE but before surgery. Blood flow changes were analyzed with the Wilcoxon signed rank test, and correlations with Spearman rank correlation. Results The 0-day group included 24 participants (median age, 72 years [IQR, 69-77 years]; 17 male participants), and the 3-day group included 13 participants (median age, 71 years [IQR, 68-78 years]; eight male participants). Both groups showed increased left PV (LPV) flow rate after PVE (0-day group: from median 3.72 mL/sec [IQR, 2.83-4.55 mL/sec] to 9.48 mL/sec [IQR, 8.12-10.7 mL/sec], P < .001; 3-day group: from median 3.65 mL/sec [IQR, 2.14-3.79 mL/sec] to 8.16 mL/sec [IQR, 6.82-8.98 mL/sec], P < .001). LPV flow change correlated with FLR volume change relative to the number of days from PVE to presurgery CT only in the 3-day group (ρ = 0.62, P = .02; 0-day group, P = .11). The output of the regression equation for estimating presurgery FLR volume correlated with CT-measured volume (ρ = 0.78; P = .002). Conclusion Four-dimensional flow MRI demonstrated increased blood flow in residual portal branches 3-4 days after PVE, offering insights for estimating presurgery FLR volume. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Roldán-Alzate and Oechtering in this issue.

DOI： 10.1148/radiol.230709

Fluid signal suppression characteristics of 3D-FLAIR with a T2 selective inversion pulse in the skull base Reviewed Open Access

Shinji Naganawa, Yutaka Kato, Tadao Yoshida, Michihiko Sone

NATURE COMMUNICATIONS Vol. 14 ( 1 ) page： 4915 2023.8

From pituitary adenoma to PitNET: it is time to discuss PitNET/pituitary adenoma. Reviewed Open Access

Yasutaka Fushimi, Toshiaki Taoka, Shinji Naganawa

Japanese journal of radiology Vol. 41 ( 8 ) page： 787 - 788 2023.8

Prognostic impact of EGFR/ALK alterations in leptomeningeal metastasis from lung adenocarcinoma treated with whole-brain radiotherapy. Reviewed International journal

Hidekazu Oyoshi, Hidenari Hirata, Yasuhiro Hirano, Sadamoto Zenda, Yuzheng Zhou, Kento Tomizawa, Takeshi Fujisawa, Masaki Nakamura, Hidehiro Hojo, Atsushi Motegi, Shun-Ichiro Kageyama, Yoshitaka Zenke, Koichi Goto, Shunichi Ishihara, Shinji Naganawa, Tetsuo Akimoto

Clinical & experimental metastasis Vol. 40 ( 5 ) page： 407 - 413 2023.7

Language：English Publishing type：Research paper (scientific journal)

The prognosis and prognostic factors of patients receiving whole-brain radiotherapy (WBRT) for leptomeningeal metastasis (LM) from lung adenocarcinoma have not been established. Particularly, the impact of EGFR mutations and ALK rearrangements on survival remains unclear. This retrospective study evaluated the prognosis and prognostic factors of patients receiving WBRT for LM. We evaluated overall survival (OS) from WBRT initiation and clinical variables in 80 consecutive patients receiving WBRT for LM from lung adenocarcinoma at our institution between June 2013 and June 2021. After a median follow-up of 5.2 (range 0.5-56.5) months, the median OS was 6.2 months (95% CI 4.4-12.4). Of the 80 patients, 51 were classified as EGFR/ALK mutant (EGFR: 44; ALK: 6; both: 1) and 29 as wild-type. The median OS was 10.4 (95% CI 5.9-20.9) versus 3.8 (95% CI 2.5-7.7) months in the EGFR/ALK-mutant versus wild-type patients (HR = 0.49, P = 0.0063). Multivariate analysis indicated that EGFR/ALK alterations (HR = 0.54, P = 0.021) and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-1 (HR = 0.25, P < 0.001) were independent factors associated with favorable OS. Among the patients who underwent brain MRI before and after WBRT, intracranial progression-free survival was longer in the 26 EGFR/ALK-mutant than 13 wild-type patients (HR = 0.31, P = 0.0039). Although the prognosis of patients receiving WBRT for LM remains poor, EGFR/ALK alterations and good ECOG PS may positively impact OS in those eligible for WBRT.

DOI： 10.1007/s10585-023-10225-7