Cancer Research and Treatment

Original Articles

Novel Bronchoscopy Method for Molecular Profiling of Lung Cancer: Targeted Washing Technique: Mi-Hyun Kim, Hayoung Seong, Hyojin Jang, Saerom Kim, Wanho Yoo, Soo Han Kim, Jeongha Mok, Kwangha Lee, Ki Uk Kim, Min Ki Lee, Jung Seop Eom; Received November 25, 2024 Accepted February 25, 2025 Published online February 26, 2025; DOI: https://doi.org/10.4143/crt.2024.1128 [Accepted]

Abstract PDF: Purpose
There have been efforts to find alternative samples other than standard samples of tissue or plasma for mutational analyses for lung cancer patients. However, no other sample or technique has replaced the mutational analyses using standard samples. In this prospective study, we assessed a novel bronchoscopy method, named as targeted washing technique, for detecting the EGFR mutation.
Materials and Methods
A 3.0-mm ultrathin bronchoscope was precisely navigated to the target lung lesion with the assistance of virtual bronchoscopic navigation and fluoroscopy. Once the bronchoscope is placed in front of target lung lesion, 0.9% normal saline was instilled for targeted washing. EGFR testing using targeted washing fluid (TWF) was compared to standard methods using plasma or tumor tissue.
Results
In 41 TWF samples, the T790M mutation was detected in tissue, plasma, and TWF samples at rates of 22%, 10%, and 29%, respectively. The overall EGFR T790M detection rate using tissue, plasma, or TWF samples was 37%, with TWF samples increasing the T790M mutation detection rate by up to 10%. The accuracy of T790M mutation detection using TWF sample was 83% compared with standard samples. Four patients were found to have the EGFR T790M mutation solely through EGFR testing using TWF, which repeated rebiopsies using either plasma or tissue finally confirmed to have the T790M mutation.
Conclusion
We demonstrated the clinical potential of targeted washing technique for molecular testing, which can be a good option to overcome spatial heterogeneity, low sensitivity of plasma sample or technical limitations in collecting tumor tissues.

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Lung and Thoracic cancer

Development of the Korean Association for Lung Cancer Clinical Practice Guidelines: Recommendations on Radial Probe Endobronchial Ultrasound for Diagnosing Lung Cancer - An Updated Meta-Analysis: Soo Han Kim, Hyun Sung Chung, Jinmi Kim, Mi-Hyun Kim, Min Ki Lee, Insu Kim, Jung Seop Eom; Cancer Res Treat. 2024;56(2):464-483. Published online November 29, 2023; DOI: https://doi.org/10.4143/crt.2023.749

Abstract PDF Supplementary Material PubReader ePub: Purpose
Radial probe endobronchial ultrasound (RP-EBUS) accurately locates peripheral lung lesions (PLLs) during transbronchial biopsy (TBB). We performed an updated meta-analysis of the diagnostic yield of TBB for PLLs using RP-EBUS to generate recommendations for the development of the Korean Association of Lung Cancer guidelines.
Materials and Methods
We systematically searched MEDLINE and EMBASE (from January 2013 to December 2022), and performed a meta-analysis using R software. The diagnostic yield was evaluated by dividing the number of successful diagnoses by the total lesion number. Subgroup analysis was performed to identify related factors.
Results
Forty-one studies with a total of 13,133 PLLs were included. The pooled diagnostic yield of RP-EBUS was 0.72 (95% confidence interval [CI], 0.70 to 0.75). Significant heterogeneity was observed among studies (χ²=292.38, p < 0.01, I²=86.4%). In a subgroup analysis, there was a significant difference in diagnostic yield based on RP-EBUS findings (within, adjacent to, invisible), with a risk ratio of 1.45 (95% CI, 1.23 to 1.72) between within and adjacent to, 4.20 (95% CI, 1.89 to 9.32) between within and invisible, and 2.59 (95% CI, 1.32 to 5.01) between adjacent to and invisible. There was a significant difference in diagnostic yield based on lesion size, histologic diagnosis, computed tomography (CT) bronchus sign, lesion character, and location from the hilum. The overall complication rate of TBB with RP-EBUS was 6.8% (bleeding, 4.5%; pneumothorax, 1.4%).
Conclusion
Our study showed that TBB with RP-EBUS is an accurate diagnostic tool for PLLs with good safety profiles, especially for PLLs with within orientation on RP-EBUS or positive CT bronchus sign.

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Should We Perform Repeated Re-biopsy for the Detection of T790M Mutation?: Saerom Kim, Soo Han Kim, Jinmi Kim, Mi-Hyun Kim, Min Ki Lee, Jung Seop Eom; Cancer Res Treat. 2023;55(4):1190-1197. Published online April 17, 2023; DOI: https://doi.org/10.4143/crt.2023.320

Abstract PDF PubReader ePub

Purpose
Epidermal growth factor receptor (EGFR) T790M mutations have been detected in the second or third rebiopsy, even if the T790M mutation was not identified in the first rebiopsy. This meta-analysis investigated the EGFR T790M mutation detection rates and its additional advantages with repeated rebiopsies.
Materials and Methods
We searched through the PubMed and EMBASE databases up to June 2022. Studies reporting rebiopsy to identify the EGFR T790M mutation in case of disease progression among patients with advanced non-small cell lung cancer and multiple rebiopsies were included. The quality of the included studies was checked using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool.
Results
Eight studies meeting the eligibility criteria, reporting 1,031 EGFR mutation–positive patients were selected. The pooled EGFR T790M mutation detection rate of the first and repeated rebiopsies were 0.442 (95% confidence interval [CI], 0.411 to 0.473; I²=84%; p < 0.01) and 0.465 (95% CI, 0.400 to 0.530; I²=69%; p < 0.01), respectively. Overall, the pooled detection rate of EGFR T790M mutation was 0.545 (95% CI, 0.513 to 0.576), which increased by 10.3% with repeated rebiopsies.
Conclusion
This meta-analysis identified that repeated rebiopsy increases the detection rate of EGFR T790M mutation by 10.3%, even if EGFR T790M mutation is not detected in the first rebiopsy. Our results indicate that the spatiotemporal T790M heterogeneity can be overcome with repeated rebiopsy.

Citations

Citations to this article as recorded by

Clinical utility of repeated rebiopsy for EGFR T790M mutation detection in non-small cell lung cancer
Eun Hye Lee, Se Hyun Kwak, Kyeong Yeon Kim, Chi Young Kim, Sang Hoon Lee, Seok-Jae Heo, Yoon Soo Chang, Eun Young Kim
Frontiers in Oncology.2024;[Epub] CrossRef
Repeated rebiopsy for detection of EGFR T790M mutation in patients with advanced-stage lung adenocarcinoma: Associated factors and treatment outcomes of Osimertinib
Taeyun Kim, Junsu Choe, Sun Hye Shin, Byeong-Ho Jeong, Kyungjong Lee, Hojoong Kim, Se-Hoon Lee, Sang-Won Um, Hamidreza Montazeri Aliabadi
PLOS ONE.2024; 19(9): e0310079. CrossRef
Rebiopsie tumorale : quand ? pour qui ? pourquoi ? comment ?
V. Fallet
Revue des Maladies Respiratoires Actualités.2023; 15(2): 2S121. CrossRef

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3 Crossref

The Additive Impact of Transbronchial Cryobiopsy Using a 1.1-mm Diameter Cryoprobe on Conventional Biopsy for Peripheral Lung Nodules: Soo Han Kim, Jeongha Mok, Eun-Jung Jo, Mi-Hyun Kim, Kwangha Lee, Ki Uk Kim, Hye-Kyung Park, Min Ki Lee, Jung Seop Eom; Cancer Res Treat. 2023;55(2):506-512. Published online November 1, 2022; DOI: https://doi.org/10.4143/crt.2022.1008

Abstract PDF Supplementary Material PubReader ePub

Purpose
The diagnostic yield of transbronchial biopsy (TBB) using radial probe endobronchial ultrasound (RP-EBUS) is 71%, which is lower than that of transthoracic needle biopsy. We investigated the performance and safety of sequential transbronchial cryobiopsy (TBC) using a novel 1.1-mm diameter cryoprobe, after conventional TBB using RP-EBUS for the diagnosis of peripheral lung lesions (PLLs).
Materials and Methods
From April 2021 to November 2021, 110 patients who underwent bronchoscopy using RP-EBUS for the diagnosis of PLL ≤ 30 mm were retrospectively included in our study. All records were followed until June 2022.
Results
The overall diagnostic yield of combined TBB and TBC was 79.1%, which was higher than 60.9% of TBB alone (p=0.005). The diagnostic yield of sequential TBC was 65.5%, which increased the overall diagnostic yield by 18.2%. The surface area of tissues by TBC (mean area, 18.5 mm²) was significantly larger than those of TBB by 1.5-mm forceps (3.4 mm², p < 0.001) and 1.9-mm forceps (3.7 mm², p=0.011). In the multivariate analysis, PLLs with the longest diameter of ≤ 22 mm were found to be related to additional diagnostic benefits from sequential TBC (odds ratio, 3.51; 95% confidence interval, 1.043 to 11.775; p=0.042). Complications were found in 10.5% of the patients: pneumothorax (1.0%), infection (1.0%), and significant bleeding (8.6%). None of the patients developed any life-threatening complications.
Conclusion
Sequential TBC with a 1.1-mm cryoprobe improved the performance of conventional TBB using RP-EBUS without serious complications.

Citations

Citations to this article as recorded by

Transbronchial lung cryobiopsy for peripheral pulmonary lesions. A narrative review
Y. Tang, S. Tian, H. Chen, X. Li, X. Pu, X. Zhang, Y. Zheng, Y. Li, H. Huang, C. Bai
Pulmonology.2024; 30(5): 475. CrossRef
Transbronchial Tumor Ablation
Russell Miller, George Cheng
Current Pulmonology Reports.2024; 13(1): 103. CrossRef
Using cryoprobes of different sizes combined with cone-beam computed tomography-derived augmented fluoroscopy and endobronchial ultrasound to diagnose peripheral pulmonary lesions: a propensity-matched study
Ching-Kai Lin, Sheng-Yuan Ruan, Hung-Jen Fan, Hao-Chun Chang, Yen-Ting Lin, Chao-Chi Ho
Respiratory Research.2024;[Epub] CrossRef
Next‐generation sequencing using tissue specimen collected with a 1.1 mm‐diameter cryoprobe in patients with lung cancer
Mi‐Hyun Kim, Soo Han Kim, Geewon Lee, Jeongha Mok, Min Ki Lee, Ju Sun Song, Jung Seop Eom
Respirology.2024; 29(4): 333. CrossRef
Development of the Korean Association for Lung Cancer Clinical Practice Guidelines: Recommendations on Radial Probe Endobronchial Ultrasound for Diagnosing Lung Cancer - An Updated Meta-Analysis
Soo Han Kim, Hyun Sung Chung, Jinmi Kim, Mi-Hyun Kim, Min Ki Lee, Insu Kim, Jung Seop Eom
Cancer Research and Treatment.2024; 56(2): 464. CrossRef
Navigational bronchoscopy with tranbronchial cryobiopsy in differential diagnosis of peripheral pulmonary lesions
Ya.O. Chesalina, I.Yu. Shabalina, L.A. Semenova, I.V. Sivokozov
Pirogov Russian Journal of Surgery.2024; (6): 36. CrossRef
Advanced Bronchoscopic Diagnostic Techniques in Lung Cancer
Dongil Park
Tuberculosis and Respiratory Diseases.2024; 87(3): 282. CrossRef
Clinical utility of rapid on-site evaluation of brush cytology during bronchoscopy using endobronchial ultrasound with a guide sheath
Kazuhiro Nishiyama, Kei Morikawa, Shotaro Kaneko, Makoto Nishida, Aya Matsushima, Yoshihiro Nishi, Yu Numata, Yusuke Shinozaki, Hajime Tsuruoka, Hirotaka Kida, Hiroshi Handa, Naoki Shimada, Chie Okawa, Nobuyuki Ohike, Junki Koike, Masamichi Mineshita
Scientific Reports.2024;[Epub] CrossRef
Bronchial branch tracing navigation in ultrathin bronchoscopy-guided radial endobronchial ultrasound for peripheral pulmonary nodule
Sze Shyang Kho, Shirin Hui Tan, Swee Kim Chan, Chan Sin Chai, Siew Teck Tie
BMC Pulmonary Medicine.2024;[Epub] CrossRef
The diagnosis of peripheral lung lesions: transbronchial biopsy using a radial probe endobronchial ultrasound
Jung Seop Eom
Journal of the Korean Medical Association.2023; 66(3): 166. CrossRef
Clinical outcomes of transbronchial cryobiopsy using a 1.1-mm diameter cryoprobe for peripheral lung lesions - A prospective pilot study
Soo Han Kim, Jeongha Mok, Saerom Kim, Wan Ho Yoo, Eun-Jung Jo, Mi-Hyun Kim, Kwangha Lee, Ki Uk Kim, Hye-Kyung Park, Min Ki Lee, Jung Seop Eom
Respiratory Medicine.2023; 217: 107338. CrossRef

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Real-World Study of Osimertinib in Korean Patients with Epidermal Growth Factor Receptor T790M Mutation–Positive Non–Small Cell Lung Cancer: Jang Ho Lee, Eun Young Kim, Cheol-Kyu Park, Shin Yup Lee, Min ki Lee, Seong-Hoon Yoon, Jeong Eun Lee, Sang Hoon Lee, Seung Joon Kim, Sung Yong Lee, Jun Hyeok Lim, Tae-Won Jang, Seung Hun Jang, Kye Young Lee, Seung Hyeun Lee, Sei Hoon Yang, Dong Won Park, Chan Kwon Park, Hye Seon Kang, Chang Dong Yeo, Chang-Min Choi, Jae Cheol Lee; Cancer Res Treat. 2023;55(1):112-122. Published online July 19, 2022; DOI: https://doi.org/10.4143/crt.2022.381

Abstract PDF Supplementary Material PubReader ePub

Purpose
Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation–positive non–small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment. Herein, we report on the use of osimertinib in patients with EGFR T790M mutation–positive non–small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea.
Materials and Methods
Patients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints.
Results
A total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval [CI], 13.0 to 16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1 to 15.9). The median overall survival was 36.7 months (95% CI, 30.9 to not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten patients (1.8%), including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects.
Conclusion
Osimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation–positive in Korean patients with no new safety signals.

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The importance of re-biopsy in the era of molecular therapy for lung cancer
Nensi Lalic, Daliborka Bursac, Marko Bojovic, Marko Nemet, Ivan Ergelasev
Srpski arhiv za celokupno lekarstvo.2024; 152(3-4): 209. CrossRef
Detection of EGFR exon 20 insertion mutations in non-small cell lung cancer: implications for consistent nomenclature in precision medicine
Jieun Park, Boram Lee, Ji-Young Song, Minjung Sung, Mi Jeong Kwon, Chae Rin Kim, Sangjin Lee, Young Kee Shin, Yoon-La Choi
Pathology.2024; 56(5): 653. CrossRef
Real‐world study of lazertinib as second‐line or greater treatment in advanced non‐small cell lung cancer
Jeong Uk Lim, Kyuhwan Kim, Kyu Yean Kim, Hye Seon Kang, Ah. Young Shin, Chang Dong Yeo, Sung Kyoung Kim, Chan Kwon Park, Sang Haak Lee, Seung Joon Kim
Thoracic Cancer.2024; 15(19): 1513. CrossRef
Comparative effectiveness of lazertinib in patients with EGFR T790M-positive non-small-cell lung cancer using a real-world external control
Ha-Lim Jeon, Meesong Kwak, Sohee Kim, Hye-Yeon Yu, Ju-Young Shin, Hyun Ae Jung
Scientific Reports.2024;[Epub] CrossRef
A Randomized, Multi-Center, Open Label Study to Compare the Safety and Efficacy between Afatinib Monotherapy and Combination Therapy with HAD-B1 for the Locally Advanced or Metastatic NSCLC Patients with EGFR Mutations
Eunbin Kwag, Soo-Dam Kim, Seong-Hoon Shin, Chulho Oak, So-Jung Park, Jun-Yong Choi, Seong Hoon Yoon, In-Cheol Kang, Mi-Kyung Jeong, Hyun Woo Lee, Sun-Hwi Bang, Ji Woong Son, Sanghun Lee, Seung Joon Kim, Hwa-Seung Yoo
Integrative Cancer Therapies.2024;[Epub] CrossRef
Clinical utility of repeated rebiopsy for EGFR T790M mutation detection in non-small cell lung cancer
Eun Hye Lee, Se Hyun Kwak, Kyeong Yeon Kim, Chi Young Kim, Sang Hoon Lee, Seok-Jae Heo, Yoon Soo Chang, Eun Young Kim
Frontiers in Oncology.2024;[Epub] CrossRef
Real-world evidence of osimertinib in Chinese patients with EGFR T790M-positive non-small cell lung cancer: a subgroup analysis from ASTRIS study
Qing Zhou, He-Long Zhang, Li-Yan Jiang, Yuan-Kai Shi, Yuan Chen, Jin-Ming Yu, Cai-Cun Zhou, Yong He, Yan-Ping Hu, Zong-An Liang, Yue-Yin Pan, Wen-Lei Zhuo, Yong Song, Gang Wu, Gong-Yan Chen, You Lu, Cui-Ying Zhang, Yi-Ping Zhang, Ying Cheng, Shun Lu, Chan
Journal of Cancer Research and Clinical Oncology.2023; 149(12): 10771. CrossRef

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Development of Protocol for Korean Lung Cancer Screening Project (K-LUCAS) to Evaluate Effectiveness and Feasibility to Implement National Cancer Screening Program: Jaeho Lee, Juntae Lim, Yeol Kim, Hyae Young Kim, Jin Mo Goo, Choon-Taek Lee, Seung Hun Jang, Won-Chul Lee, Chan Wha Lee, Jin Young An, Ki Dong Ko, Min Ki Lee, Kui Son Choi, Boyoung Park, Duk Hyoung Lee; Cancer Res Treat. 2019;51(4):1285-1294. Published online February 19, 2019; DOI: https://doi.org/10.4143/crt.2018.464

Abstract PDF PubReader ePub

Purpose
To reduce lung cancer mortality, lung cancer screening was recommended using low-dose computed tomography (LDCT) to high-risk population. A protocol for multicenter lung cancer screening pilot project was developed to evaluate the effectiveness and feasibility of lung cancer screening to implement National Cancer Screening Program in Korea.
Materials and Methods
Multidisciplinary expert committee was comprised to develop a standardized protocol for Korean Lung Cancer Screening Project (K-LUCAS). K-LUCAS is a population-based single arm trial that targets high-risk population aged 55-74 years with at least 30 pack-year smoking history. LDCT results are reported by Lung-RADS suggested by American Radiology Society. Network-based system using computer-aided detection program is prepared to assist reducing diagnostic errors. Smoking cessation counselling is provided to all currently smoking participants. A small pilot test was conducted to check the feasibility and compliance of the protocols for K-LUCAS.
Results
In pilot test, 256 were participated. The average age of participants was 63.2 years and only three participants (1.2%) were female. The participants had a smoking history of 40.5 pack-year on average and 53.9% were current smokers. Among them, 86.3% had willing to participate in lung cancer screening again. The average willingness to quit smoking among current smokers was 12.7% higher than before screening. In Lung-RADS reports, 10 (3.9%) were grade 3 and nine (3.5%) were grade 4. One participant was diagnosed as lung cancer.
Conclusion
The protocol developed by this study is assessed to be feasible to perform K-LUCAS in multicenter nationwide scale.

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Metabolic Burden Measured by ¹⁸F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Is a Prognostic Factor in Patients with Small Cell Lung Cancer: Mi-Hyun Kim, Ji Seok Lee, Jeong Ha Mok, Kwangha Lee, Ki Uk Kim, Hye-Kyung Park, Seong-Jang Kim, Min Ki Lee; Cancer Res Treat. 2014;46(2):165-171. Published online April 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.2.165

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Purpose

Evidence regarding the usefulness of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in predicting the prognosis of non-small cell lung cancer is increasing. However, data on small cell lung cancer (SCLC) are scarce. The aim of this study was to evaluate the prognostic value of metabolic parameters measured using ¹⁸F-FDG PET/CT in patients with SCLC.

Materials and Methods

We conducted a retrospective review of 114 patients with pathologically proven SCLC (26 cases of limited disease and 88 cases of extensive disease) who underwent pretreatment ¹⁸F-FDG PET/CT. The maximal SUV (SUV_max) was used quantitatively for determination of FDG PET activity. The SUV_max of the primary tumor (primary SUV_max), the sum of SUV_max values of malignant lesions (SUV_sum), and the mean SUV_max of malignant lesions were calculated.

Results

The patient population was subdivided using a median SUV_sum value of 24.6. High SUV_sum showed a significant association with known factors for poor prognosis, including higher neuron-specific enolase (p=0.010), CYFRA 21-1 (p=0.014), and extensive disease status (p=0.007). Patients with high SUV_sum had significantly shorter median overall survival (6.6 months vs. 13.0 months, p<0.001) and progression-free survival (5.2 months vs. 8.0 months, p<0.001) than patients with low SUV_sum. Results of multivariate analysis showed that SUV_sum, chemotherapy cycles, and the response to first-line treatment were significant prognostic factors of survival. In contrast, mean SUV_max and primary SUV_max were not significant predictors of survival.

Conclusion

In this study, metabolic burden represented by SUV_sum from pretreatment ¹⁸F-FDG PET/CT was an independent prognostic factor in patients with SCLC.

Citations

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Prognostic value of metabolic parameters on baseline 18F-FDG PET/CT in small cell lung cancer
Mine ARAZ, Cigdem SOYDAL, Elgin ÖZKAN, Elif SEN, Demet NAK, Ozlem N. KUCUK, Ugur GÖNÜLLÜ, K. Metin KIR
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Prognostic Value of 18F–FDG–PET Parameters in Patients with Small Cell Lung Cancer: A Meta-Analysis and Review of Current Literature
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Cem Mirili, Isa Burak Guney, Semra Paydas, Gulsah Seydaoglu, Tuba Korkmaz Kapukaya, Ali Ogul, Serkan Gokcay, Mahmut Buyuksimsek, Abdullah Evren Yetisir, Bilgin Karaalioglu, Mert Tohumcuoglu
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Case Report

Sarcoidosis Mimicking Cancer Metastasis Following Chemotherapy for Ovarian Cancer: Mi Hyun Kim, Kwangha Lee, Ki Uk Kim, Hye-Kyung Park, Min Ki Lee, Dong Soo Suh; Cancer Res Treat. 2013;45(4):354-358. Published online December 31, 2013; DOI: https://doi.org/10.4143/crt.2013.45.4.354

Abstract PDF PubReader ePub

We report on a rare case of sarcoidosis that developed after chemotherapy for ovarian cancer, and mimicked a cancer metastasis. A 52-year-old female diagnosed with stage III ovarian cancer underwent curative surgery and postoperative chemotherapy. Four months later, her whole-body positron emission tomography and computed tomography (CT) scan showed high uptake in the mediastinal lymph nodes, and ovarian cancer recurrence was suspected. Biopsy of the mediastinal lymph nodes and subcutaneous nodules revealed noncaseating granulomas. These lesions resolved spontaneously without treatment; however, newly developed perilymphatic and centrilobular nodules were observed on follow-up chest CT. Surgical biopsy of these lesions also showed noncaseating granulomas. She was finally diagnosed with sarcoidosis.

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