Cancer Research and Treatment

Original Articles

Lung and Thoracic cancer

Adjuvant Pembrolizumab in Patients with Stage IIIA/N2 Non–Small Cell Lung Cancer Completely Resected after Neoadjuvant Concurrent Chemoradiation: A Prospective, Open-Label, Single-Arm, Phase 2 Trial: Junghoon Shin, Sehhoon Park, Kyung Hwan Kim, Eui-Cheol Shin, Hyun Ae Jung, Jong Ho Cho, Jong-Mu Sun, Se-Hoon Lee, Yong Soo Choi, Jin Seok Ahn, Jhingook Kim, Keunchil Park, Young Mog Shim, Hong Kwan Kim, Jae Myoung Noh, Yong Chan Ahn, Hongryull Pyo, Myung-Ju Ahn; Cancer Res Treat. 2024;56(4):1084-1095. Published online April 30, 2024; DOI: https://doi.org/10.4143/crt.2024.084

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Purpose
Optimal treatment for stage IIIA/N2 non–small cell lung cancer (NSCLC) is controversial. We aimed to assess the efficacy and safety of adjuvant pembrolizumab for stage IIIA/N2 NSCLC completely resected after neoadjuvant concurrent chemoradiation therapy (CCRT).
Materials and Methods
In this open-label, single-center, single-arm phase 2 trial, patients with stage IIIA/N2 NSCLC received adjuvant pembrolizumab for up to 2 years after complete resection following neoadjuvant CCRT. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS) and safety. As an exploratory biomarker analysis, we evaluated the proliferative response of blood CD39⁺PD-1⁺CD8⁺ T cells using fold changes in the percentage of proliferating Ki-67⁺ cells from days 1 to 7 of cycle 1 (Ki-67_D7/D1).
Results
Between October 2017 and October 2018, 37 patients were enrolled. Twelve (32%) and three (8%) patients harbored EGFR and ALK alterations, respectively. Of 34 patients with programmed cell death ligand 1 assessment, 21 (62%), nine (26%), and four (12%) had a tumor proportion score of < 1%, 1%-50%, and ≥ 50%, respectively. The median follow-up was 71 months. The median DFS was 22.4 months in the overall population, with a 5-year DFS rate of 29%. The OS rate was 86% at 2 years and 76% at 5 years. Patients with tumor recurrence within 6 months had a significantly lower Ki-67D7/D1 among CD39⁺PD-1⁺CD8⁺ T cells than those without (p=0.036). No new safety signals were identified.
Conclusion
Adjuvant pembrolizumab may offer durable disease control in a subset of stage IIIA/N2 NSCLC patients after neoadjuvant CCRT and surgery.

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Adjuvant immunotherapy improves survival in completely resected stage IB–III NSCLC: a systematic review and meta-analysis
Hong Huang, Pengchen Bao, Hongyu Jin, Wenyang Li, Hui Shen, Zhen Qin, Ying Pan, Xinming Su, Delei Kong
Frontiers in Oncology.2025;[Epub] CrossRef
Advances in molecular pathology and therapy of non-small cell lung cancer
Qing Huang, Yuanxiang Li, Yingdan Huang, Jingyi Wu, Wendai Bao, Chang Xue, Xiaoyu Li, Shuang Dong, Zhiqiang Dong, Sheng Hu
Signal Transduction and Targeted Therapy.2025;[Epub] CrossRef

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Genitourinary cancer

Neoadjuvant Cisplatin-Based Chemotherapy Followed by Selective Bladder Preservation Chemoradiotherapy in Muscle-Invasive Urothelial Carcinoma of the Bladder: Post Hoc Analysis of Two Prospective Studies: Sung Wook Cho, Sung Hee Lim, Ghee Young Kwon, Chan Kyo Kim, Won Park, Hongryull Pyo, Jae Hoon Chung, Wan Song, Hyun Hwan Sung, Byong Chang Jeong, Se Hoon Park; Cancer Res Treat. 2024;56(3):893-897. Published online February 15, 2024; DOI: https://doi.org/10.4143/crt.2024.015

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Purpose
Bladder preservation chemoradiotherapy (CRT) in patients with a clinical complete response (cCR) following cisplatin-based neoadjuvant chemotherapy (NAC) is a promising treatment strategy for muscle-invasive bladder urothelial carcinoma (MIBC). A combined analysis of raw data from two prospective phase II studies was performed to better evaluate the feasibility of selective bladder preservation CRT.
Materials and Methods
The analysis was based on primary efficacy data from two independent studies, including 76 MIBC patients receiving NAC followed by bladder preservation CRT. The efficacy data included metastasis-free survival (MFS) and disease-free survival (DFS). For the present analysis, starting point of survival was defined as the date of commencing CRT.
Results
Among 76 patients, 66 had a cCR following NAC. Sixty-four patients received gemcitabine and cisplatin (GC) combination chemotherapy in neoadjuvant setting, and 12 received nivolumab plus GC. Bladder preservation CRT following NAC was generally well-tolerated, with low urinary tract symptoms being the most common late complication. With a median follow-up of 64 months, recurrence was recorded in 43 patients (57%): intravesical only (n=20), metastatic only (n=16), and both (n=7). In 27 patients with intravesical recurrence, transurethral resection, and Bacillus Calmette-Guerin treatment was given to 17 patients. Salvage cystectomy was performed in 10 patients. Median DFS was 46.3 (95% confidence interval [CI], 25.1 to 67.5) months, and the median MFS was not reached. Neither DFS nor MFS appeared to be affected by any of the baseline characteristics. However, DFS was significantly longer in patients with a cCR than in those without (hazard ratio, 0.465; 95% CI, 0.222 to 0.976).
Conclusion
The strategy of NAC followed by selective bladder preservation CRT based on the cCR is feasible in the treatment of MIBC. A standardized definition of cCR is needed to better assess disease status post-NAC.

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News and prospects on radiotherapy for bladder cancer: Is trimodal therapy becoming the gold standard?
Olivier Riou, Christophe Hennequin, Jonathan Khalifa, Paul Sargos
Cancer/Radiothérapie.2024; 28(6-7): 623. CrossRef

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Lung and Thoracic cancer

The Incidence and Risk Factors of Chronic Pulmonary Infection after Radiotherapy in Patients with Lung Cancer: Yeonseok Choi, Jae Myoung Noh, Sun Hye Shin, Kyungjong Lee, Sang-Won Um, Hojoong Kim, Hongryull Pyo, Yong Chan Ahn, Byeong-Ho Jeong; Cancer Res Treat. 2023;55(3):804-813. Published online January 3, 2023; DOI: https://doi.org/10.4143/crt.2022.1305

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Purpose
This study aimed to investigate cumulative incidence and risk factors associated with chronic pulmonary infection (CPI) development after radiotherapy for lung cancer.
Materials and Methods
We retrospectively analyzed 1,872 patients with lung cancer who received radiotherapy for lung cancer from 2010-2014, had a follow-up period of ≥ 3 months after radiotherapy, and did not have CPI at the time of radiotherapy. CPI was defined as pulmonary tuberculosis, non-tuberculous mycobacterial pulmonary disease, chronic pulmonary aspergillosis, or pulmonary actinomycosis. The cumulative incidence of CPI and overall survival (OS) were estimated using the Kaplan-Meier method, and a multivariable Cox proportional hazards analysis was performed to identify risk factors associated with CPI development.
Results
The median follow-up period was 2.3 years with OS rates of 55.6% and 37.6% at 2 and 5 years, respectively. CPI developed in 59 patients at a median of 1.8 years after radiotherapy, with cumulative incidence rates of 1.1%, 3.4%, 5.0%, and 6.8% at 1, 3, 5, and 7 years, respectively. A lower body mass index, interstitial lung disease, prior pulmonary tuberculosis, larger clinical target volume, history of lung cancer surgery or radiation pneumonitis, and use of inhaled corticosteroids were independent risk factors for CPI development.
Conclusion
The long-term survival rate of lung cancer patients receiving radiotherapy was not low, but the cumulative incidence of CPI gradually increased to 6.8% at 7 years after radiotherapy. Therefore, close monitoring of CPI development is required in surviving patients with risk factors.

Citations

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Chronic progressive pulmonary aspergillosis within the irradiated field after stereotactic body radiotherapy: two case reports
Nao Mamuro, Noriko Kishi, Yukinori Matsuo, Masahiro Yoneyama, Hiroyuki Inoo, Minoru Inoue, Takashi Mizowaki
International Cancer Conference Journal.2025; 14(2): 113. CrossRef
Predictive nomogram for risk of pulmonary infection in lung cancer patients undergoing radiochemotherapy: development and performance evaluation
Yujie Huang
American Journal of Cancer Research.2025; 15(2): 781. CrossRef
The Inter-Relationships Among the Risk Factors for Pulmonary Infection and the Diagnostic Utility of Inflammatory Markers in Patients with Non-Small Cell Lung Cancer
Wenwen Qin, Tiebin You, Tai Guo, Ruixin Tian, Xiaoman Cui, Ping Wang
Infection and Drug Resistance.2025; Volume 18: 1111. CrossRef
Incidence and predictors of pulmonary aspergillosis in patients with lung cancer: a systematic review and meta-analysis
Geling Teng, Feng Jin, Hua Zhang, Min Zhang
Frontiers in Medicine.2025;[Epub] CrossRef
Host Risk Factors for Tuberculosis
Vahid Asgharzadeh, Seyyed Amin Seyyed Rezaei, Mohammad Asgharzadeh, Jalil Rashedi, Hossein Samadi Kafil, Hossein Jalaei Nobari, Ahmad Ali Khalili, Mortaza Raeisi, Mahdi Asghari Ozma, Behroz Mahdavi Poor
Infectious Disorders - Drug Targets.2025;[Epub] CrossRef
Interaction between Dectin-1 gene polymorphisms and low weight on the risk of invasive pulmonary aspergillosis in patients with lung cancer undergoing surgery
Wenfang Jin, Yu Yao, Yanling Lv
Discover Oncology.2025;[Epub] CrossRef
Coexisting Lung Cancer and Pulmonary Tuberculosis: A Comprehensive Review From Incidence to Management
Wendi Zhou, Hongxu Lu, Jiamin Lin, Jialou Zhu, Jizhen Liang, Yalin Xie, Jinxing Hu, Ning Su
Cancer Reports.2025;[Epub] CrossRef
Invasive aspergillosis complicated in a patient with non-small cell lung cancer harboring RET fusion during treatment with RET-TKIs: a case report and literature review
Kaidiriye Setiwalidi, Yimeng Li, Yuyan Ma, Zhanpeng Hao, Yujia Zhao, Yuxin Zhang, Xuan Liang, Tao Tian, Zhiping Ruan, Yu Yao, Xiao Fu
Frontiers in Oncology.2024;[Epub] CrossRef

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Genitourinary cancer

Neoadjuvant Nivolumab Plus Gemcitabine/Cisplatin Chemotherapy in Muscle-Invasive Urothelial Carcinoma of the Bladder: Hongsik Kim, Byong Chang Jeong, Joohyun Hong, Ghee Young Kwon, Chan Kyo Kim, Won Park, Hongryull Pyo, Wan Song, Hyun Hwan Sung, Jung Yong Hong, Se Hoon Park; Cancer Res Treat. 2023;55(2):636-642. Published online October 6, 2022; DOI: https://doi.org/10.4143/crt.2022.343

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Purpose
The activity and safety of neoadjuvant nivolumab plus gemcitabine/cisplatin (N+GC) were tested in patients with muscle-invasive bladder urothelial carcinoma (MIBC).
Materials and Methods
In a prospective phase II trial, patients with cT2-T4a N0 MIBC who were eligible for cisplatin and medically appropriate to undergo radical cystectomy (RC) were enrolled. Treatment with nivolumab 3 mg/kg on days 1 and 15 plus GC (cisplatin 70 mg/m2 on day 1, and gemcitabine 1,000 mg/m2 on days 1, 8, and 15) was repeated every 28 days up to 3 or 4 cycles, depending on the surgery schedules. The primary endpoint was pathologic complete response (pCR, ypT0). Secondary endpoints included pathologic downstaging (≤ ypT1), disease-free survival (DFS), and safety.
Results
Between September 2019 and October 2020, 51 patients were enrolled. Neoadjuvant N+GC was well tolerated. Among 49 patients who completed neoadjuvant N+GC, clinical complete response (cCR) was achieved in 59% of intent-to-treat (ITT) population. RC was performed in 34 (69%) patients. pCR was achieved in 24% (12/49) of ITT population and 35% (12/34) of RC patients. Median DFS was not reached. Over a median follow-up of 24 months, 12 patients experienced disease recurrence and were treated with palliative therapy or surgery. Although 12 patients declined surgery and were treated with concurrent chemoradiotherapy, DFS was longer in patients with cCR after neoadjuvant therapy than those without. Preoperative programmed death-ligand 1 (PD-L1) did not correlate with pCR or pathologic downstaging rates.
Conclusion
Neoadjuvant N+GC was feasible and provided meaningful pathologic responses in patients with MIBC, regardless of baseline PD-L1 expression (ONO-4538-X41; CRIS.nih.go.kr, KCT0003804).

Citations

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Evaluating Neoadjuvant Immunochemotherapeutic Response for Bladder Carcinoma Using Amide Proton Transfer-Weighted MRI
Lingmin Kong, Bei Weng, Qian Cai, Ling Ma, Wenxin Cao, Yanling Chen, Long Qian, Yan Guo, Junxing Chen, Huanjun Wang
Academic Radiology.2025; 32(4): 2090. CrossRef
Current and Future Role of Circulating DNA in the Diagnosis and Management of Urothelial Carcinoma
Joaquim Bellmunt, Brian M. Russell, Bernadett Szabados, Begoña P. Valderrama, Rosa Nadal
American Society of Clinical Oncology Educational Book.2025;[Epub] CrossRef
Comparison of neoadjuvant chemotherapy and combined chemotherapy with immunotherapy for muscle-invasive bladder cancer: a propensity score-matched analysis
Hao Zhang
American Journal of Translational Research.2025; 17(1): 125. CrossRef
Improving Urothelial Carcinoma Outcomes: The Powerful Combination of Neoadjuvant and Adjuvant Chemotherapy in the Perioperative Period
Jincong Li, Yuxuan Song, Rui Chen, Hanlin Gao, Yang Liu, Yun Peng, Jilin Wu, Shicong Lai, Yiqing Du, Caipeng Qin, Tao Xu
Annals of Surgical Oncology.2025;[Epub] CrossRef
The practical roadmap for peri-cystectomy approaches in muscle-invasive bladder cancer
Joseph Kattan, Clarisse Kattan, Fouad Aoun, Elie Nemr
Frontiers in Oncology.2025;[Epub] CrossRef
Neoadjuvant immunotherapy for muscle-invasive bladder cancer: a 2025 update
Ilias Giannakodimos, Afroditi Ziogou, Alexios Giannakodimos, Konstantinos Tzelepis, Zisis Kratiras, Evangelos Fragkiadis, Ioannis Zachos, Vasileios Tzortzis, Michael Chrisofos, Nikolaos Charalampakis
Immunotherapy.2025; 17(6): 447. CrossRef
Oncolytic viruses: a promising therapy for malignant pleural effusion and solid tumors
Xinya Wang, Qin Zhou, Xuyan Zhang, Han Hu, Binlei Liu, Yang Wang
Frontiers in Immunology.2025;[Epub] CrossRef
Advancements in systemic therapy for muscle-invasive bladder cancer: A systematic review from the beginning to the latest updates
Takafumi Yanagisawa, Akihiro Matsukawa, Jeremy Yuen-Chun Teoh, Keiichiro Mori, Tatsushi Kawada, Satoshi Katayama, Paweł Rajwa, Fahad Quhal, Benjamin Pradere, Marco Moschini, Shahrokh F. Shariat, Jun Miki, Takahiro Kimura
Bladder Cancer.2025;[Epub] CrossRef
Impact of Immune Checkpoint Inhibitors as Neoadjuvant Therapy for Muscle-invasive Bladder Cancer: A Systematic Review, Meta-analysis, and Network Meta-analysis
Akihiro Matsukawa, Angelo Cormio, Marcin Miszczyk, Mehdi Kardoust Parizi, Tamás Fazekas, Ichiro Tsuboi, Stefano Mancon, Robert J. Schulz, Giulio Litterio, Ekaterina Laukhtina, Paweł Rajwa, Thomas Seisen, Keiichiro Mori, Francesca Sanguedolce, Andrea Bened
European Urology Oncology.2025;[Epub] CrossRef
Novel neoadjuvant therapies for muscle‐invasive bladder cancer: Systematic review and meta‐analysis
Shugo Yajima, Naoki Imasato, Hitoshi Masuda
BJUI Compass.2025;[Epub] CrossRef
Optimizing enfortumab vedotin plus pembrolizumab therapy
Elias Antoine Karam, Yaghi César Céline, Gilles Prince, Fouad Attieh, Hampig Raphael Kourie, Joseph Kattan, Elie Nemer
Oncotarget.2025; 16(1): 481. CrossRef
Efficacy and safety of neoadjuvant PD-1 inhibitors or PD-L1 inhibitors for muscle invasive bladder cancer: a systematic review and meta-analysis
Shibo Huang, Yanping Huang, Chunyan Li, Yiwen Liang, Miaoyan Huang, Raoshan Luo, Weiming Liang
Frontiers in Immunology.2024;[Epub] CrossRef
What’s new about the tumor microenvironment of urothelial carcinoma?
João Queirós Coelho, Maria João Ramos, Ridhi Ranchor, Rita Pichel, Laura Guerra, Hugo Miranda, Joana Simões, Sérgio Xavier Azevedo, Joana Febra, António Araújo
Clinical and Translational Oncology.2024; 26(7): 1549. CrossRef
A bibliometric insight into neoadjuvant chemotherapy in bladder cancer: trends, collaborations, and future avenues
Yi Huang, Chengxiao Liao, Zefeng Shen, Yitong Zou, Weibin Xie, Qinghua Gan, Yuhui Yao, JunJiong Zheng, Jianqiu Kong
Frontiers in Immunology.2024;[Epub] CrossRef
Bladder-sparing treatment using tislelizumab combined with gemcitabine/cisplatin in selected patients with muscle-invasive bladder cancer: a real-world study
Cheng Luo, Shuhang Luo, Wumier Wusimanjiang, Zongren Wang, Ping Liu, Bin Wang, Dan Yuan, Hao Lin, Abai Xu, Nan Deng, Kaihui Wu, Xuejin Zhu, Peng Xu, Junxing Chen, Bin Huang
Clinical and Translational Oncology.2024; 26(7): 1759. CrossRef
Neoadjuvant Cisplatin-Based Chemotherapy Followed by Selective Bladder Preservation Chemoradiotherapy in Muscle-Invasive Urothelial Carcinoma of the Bladder: Post Hoc Analysis of Two Prospective Studies
Sung Wook Cho, Sung Hee Lim, Ghee Young Kwon, Chan Kyo Kim, Won Park, Hongryull Pyo, Jae Hoon Chung, Wan Song, Hyun Hwan Sung, Byong Chang Jeong, Se Hoon Park
Cancer Research and Treatment.2024; 56(3): 893. CrossRef
Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer
Thomas Powles, James W.F. Catto, Matthew D. Galsky, Hikmat Al-Ahmadie, Joshua J. Meeks, Hiroyuki Nishiyama, Toan Quang Vu, Lorenzo Antonuzzo, Pawel Wiechno, Vagif Atduev, Ariel G. Kann, Tae-Hwan Kim, Cristina Suárez, Chao-Hsiang Chang, Florian Roghmann, M
New England Journal of Medicine.2024; 391(19): 1773. CrossRef
Klassische Chemotherapie, Immuntherapie oder adjuvante Strahlentherapie – Wie können wir die onkologischen Ergebnisse der radikalen Zystektomie verbessern?
Pia Paffenholz, Stefanie Zschäbitz
Die Urologie.2024; 63(10): 994. CrossRef
Recent developments in perioperative combination therapy in muscle-invasive bladder cancer
Jan-Jaap J. Mellema, Bas W.G. van Rhijn, Michiel S. van der Heijden
Current Opinion in Urology.2023; 33(5): 404. CrossRef

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General

Targeted Liquid Biopsy Using Irradiation to Facilitate the Release of Cell-Free DNA from a Spatially Aimed Tumor Tissue: Jae Myoung Noh, Yeon Jeong Kim, Ho Yun Lee, Changhoon Choi, Won-Gyun Ahn, Taeseob Lee, Hongryull Pyo, Jee Hyun Park, Donghyun Park, Woong-Yang Park; Cancer Res Treat. 2022;54(1):40-53. Published online May 25, 2021; DOI: https://doi.org/10.4143/crt.2021.151

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Purpose
We investigated the feasibility of using an anatomically localized, target-enriched liquid biopsy (TLB) in mouse models of lung cancer.
Materials and Methods
After irradiating xenograft mouse with human lung cancer cell lines, H1299 (NRAS proto-oncogene, GTPase [NRAS] Q61K) and HCC827 (epidermal growth factor receptor [EGFR] E746-750del), circulating (cell-free) tumor DNA (ctDNA) levels were monitored with quantitative polymerase chain reaction on human long interspersed nuclear element-1 and cell line-specific mutations. We checked dose-dependency at 6, 12, or 18 Gy to each tumor-bearing mouse leg using 6-MV photon beams. We also analyzed ctDNA of lung cancer patients by LiquidSCAN, a targeted deep sequencing to validated the clinical performances of TLB method.
Results
Irradiation could enhance the detection sensitivity of NRAS Q61K in the plasma sample of H1299-xenograft mouse to 4.5- fold. While cell-free DNA (cfDNA) level was not changed at 6 Gy, ctDNA level was increased upon irradiation. Using double-xenograft mouse with H1299 and HCC827, ctDNA polymerase chain reaction analysis with local irradiation in each region could specify mutation type matched to transplanted cell types, proposing an anatomically localized, TLB. Furthermore, when we performed targeted deep sequencing of cfDNA to monitor ctDNA level in 11 patients with lung cancer who underwent radiotherapy, the average ctDNA level was increased within a week after the start of radiotherapy.
Conclusion
TLB using irradiation could temporarily amplify ctDNA release in xenograft mouse and lung cancer patients, which enables us to develop theragnostic method for cancer patients with accurate ctDNA detection.

Citations

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Establishment of xenografts and methods to evaluate tumor burden for the three most frequent subclasses of pediatric-type diffuse high grade gliomas
Leire Balaguer-Lluna, Nagore G. Olaciregui, Rosario Aschero, Claudia Resa-Pares, Sonia Paco, Maria Cuadrado-Vilanova, Victor Burgueño, Merce Baulenas-Farres, Carles Monterrubio, Alejandro Manzanares, Eva Rodríguez, Cinzia Lavarino, Jaume Mora, Angel M. Ca
Journal of Neuro-Oncology.2025; 172(3): 599. CrossRef
Early Dynamics of Circulating Tumor DNA Following Curative Hypofractionated Radiotherapy Related to Disease Control in Lung Cancer
Kyungmi Yang, Jae Myoung Noh, Yeon Jeong Kim, Hongryull Pyo
Diagnostics.2025; 15(10): 1198. CrossRef
Surpassing sensitivity limits in liquid biopsy
Tina Moser, Ellen Heitzer
Science.2024; 383(6680): 260. CrossRef
Priming agents transiently reduce the clearance of cell-free DNA to improve liquid biopsies
Carmen Martin-Alonso, Shervin Tabrizi, Kan Xiong, Timothy Blewett, Sainetra Sridhar, Andjela Crnjac, Sahil Patel, Zhenyi An, Ahmet Bekdemir, Douglas Shea, Shih-Ting Wang, Sergio Rodriguez-Aponte, Christopher A. Naranjo, Justin Rhoades, Jesse D. Kirkpatric
Science.2024;[Epub] CrossRef
Treatment Response Biomarkers: Working Toward Personalized Radiotherapy for Lung Cancer
Ashley Horne, Ken Harada, Katherine D. Brown, Kevin Lee Min Chua, Fiona McDonald, Gareth Price, Paul Martin Putora, Dominic G. Rothwell, Corinne Faivre-Finn
Journal of Thoracic Oncology.2024; 19(8): 1164. CrossRef
Modulating cell-free DNA biology as the next frontier in liquid biopsies
Shervin Tabrizi, Carmen Martin-Alonso, Kan Xiong, Sangeeta N. Bhatia, Viktor A. Adalsteinsson, J. Christopher Love
Trends in Cell Biology.2024;[Epub] CrossRef
Basic Science with Preclinical Models to Investigate and Develop Liquid Biopsy: What Are the Available Data and Is It a Fruitful Approach?
Benedetta Cena, Emmanuel Melloul, Nicolas Demartines, Olivier Dormond, Ismail Labgaa
International Journal of Molecular Sciences.2022; 23(10): 5343. CrossRef
Analytical and Clinical Validation of Cell-Free Circulating Tumor DNA Assay for the Estimation of Tumor Mutational Burden
Kwang Seob Lee, Jieun Seo, Choong-Kun Lee, Saeam Shin, Zisun Choi, Seungki Min, Jun Hyuek Yang, Woo Sun Kwon, Woobin Yun, Mi Ri Park, Jong Rak Choi, Hyun Cheol Chung, Seung-Tae Lee, Sun Young Rha
Clinical Chemistry.2022; 68(12): 1519. CrossRef

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Genitourinary cancer

Risk Factors and Patterns of Locoregional Recurrence after Radical Nephrectomy for Locally Advanced Renal Cell Carcinoma: Gyu Sang Yoo, Won Park, Hongryull Pyo, Byong Chang Jeong, Hwang Gyun Jeon, Minyong Kang, Seong Il Seo, Seong Soo Jeon, Hyun Moo Lee, Han Yong Choi, Byung Kwan Park, Chan Kyo Kim, Sung Yoon Park, Ghee Young Kwon; Cancer Res Treat. 2022;54(1):218-225. Published online April 15, 2021; DOI: https://doi.org/10.4143/crt.2020.1373

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Purpose
We aimed to investigate the risk factors and patterns of locoregional recurrence (LRR) after radical nephrectomy (RN) in patients with locally advanced renal cell carcinoma (RCC).
Materials and Methods
We retrospectively analyzed 245 patients who underwent RN for non-metastatic pT3-4 RCC from January 2006 to January 2016. We analyzed the risk factors associated with poor locoregional control using Cox regression. Anatomical mapping was performed on reference computed tomography scans showing intact kidneys.
Results
The median follow-up duration was 56 months (range, 1 to 128 months). Tumor extension to renal vessels or the inferior vena cava (IVC) and Fuhrman’s nuclear grade IV were identified as independent risk factors of LRR. The 5-year actuarial LRR rates in groups with no risk factor, one risk factor, and two risk factors were 2.3%, 19.8%, and 30.8%, respectively (p < 0.001). The locations of LRR were distributed as follows: aortocaval area (n=2), paraaortic area (n=4), retrocaval area (n=5), and tumor bed (n=11). No LRR was observed above the celiac axis (CA) or under the inferior mesenteric artery (IMA).
Conclusion
Tumor extension to renal vessels or the IVC and Fuhrman’s nuclear grade IV were the independent risk factors associated with LRR after RN for pT3-4 RCC. The locations of LRR after RN for RCC were distributed in the tumor bed and regional lymphatic area from the bifurcation of the CA to that of the IMA.

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Early-Stage Renal Cell Carcinoma: Who Needs Adjuvant Therapy?
Andreea Ioana Parosanu, Cornelia Nititpir, Ioana Miruna Stanciu, Catalin Baston
Biomedicines.2025; 13(3): 543. CrossRef
Mini-subcostal incision technique for open radical nephrectomy: A practical alternative for complex renal masses
Kyle A. Blum, Chun Huang, A. Ari Hakimi, Paul Russo
Urologic Oncology: Seminars and Original Investigations.2025;[Epub] CrossRef
Survival pattern of metastatic renal cell carcinoma patients according to WHO/ISUP grade: a long-term multi-institutional study
Joongwon Choi, Seokhwan Bang, Jungyo Suh, Chang Il Choi, Wan Song, Hyeong Dong Yuk, Chan Ho Lee, Minyong Kang, Seol Ho Choo, Jung Kwon Kim, Hyung Ho Lee, Jung Ki Jo, Eu Chang Hwang, Chang Wook Jeong, Young Hwii Ko, Jae Young Park, Cheryn Song, Seong Il Se
Scientific Reports.2024;[Epub] CrossRef
Adjuvant Therapy for High-Risk Localized Renal Cell Carcinoma: Current Landscape and Future Direction
Dylan M Buller, Maria Antony, Benjamin T Ristau
OncoTargets and Therapy.2023; Volume 16: 49. CrossRef

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Salvage Concurrent Chemo-radiation Therapy for Loco-regional Recurrence Following Curative Surgery of Non-small Cell Lung Cancer: Kyung Hwa Lee, Yong Chan Ahn, Hongryull Pyo, Jae Myoung Noh, Seung Gyu Park, Tae Gyu Kim, Eonju Lee, Heerim Nam, Hyebin Lee, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park; Cancer Res Treat. 2019;51(2):769-776. Published online September 11, 2018; DOI: https://doi.org/10.4143/crt.2018.366

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Purpose
This study is to report clinical outcomes of salvage concurrent chemo-radiation therapy (CCRT) in treating patients with loco-regional recurrence (LRR) following initial complete resection of non-small cell lung cancer.
Materials and Methods
Between February 2004 and December 2016, 127 patients underwent salvage CCRT for LRR. The median radiation therapy (RT) dose was 66 Gy and clinical target volume was to cover recurrent lesion with margin without elective inclusion of regional lymphatics. Majority of patients (94.5%) received weekly platinum-based doublet chemotherapy during RT course.
Results
The median follow-up time from the start of CCRT was 25 months. The median survival duration was 49 months, and overall survival (OS) rates at 2 and 5 years were 72.9% and 43.9%. The 2- and 5-year rates of in-field failure-free survival, distant metastasis free survival, and progression free survival were 82.4% and 73.8%, 50.4% and 39.9%, and 34.6% and 22.3%, respectively. Grade ≥ 3 radiation-related esophagitis and pneumonitis occurred in 14 (11.0%) and six patients (4.7%), respectively. On both univariate and multivariate analysis, higher biologically equivalent dose (BED10) (≥ 79.2 Gy10 vs. < 79.2 Gy10; hazard ratio [HR], 0.431), smaller CTV (≤ 80 cm3 vs. > 80 cm3; HR, 0.403), and longer disease-free interval (> 1 year vs. ≤ 1 year; HR, 0.489) were significantly favorable factors for OS.
Conclusion
The current study has demonstrated that high dose salvage CCRT focused to the involved lesion only was highly effective and safe. In particular, higher BED₁₀, smaller CTV, and longer disease-free interval were favorable factors for improved survival.

Citations

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Prognosis of non‐small cell lung cancer with postoperative regional lymph node recurrence
Yoichi Ohtaki, Toshiteru Nagashima, Naoko Okano, Nobuteru Kubo, Takeru Ohtaka, Noriaki Sunaga, Reiko Sakurai, Yosuke Miura, Seshiru Nakazawa, Natsuko Kawatani, Tomohiro Yazawa, Ryohei Yoshikawa, Eiji Narusawa, Ken Shirabe
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Durvalumab after chemoradiotherapy for locoregional recurrence of completely resected non–small‐cell lung cancer (NEJ056)
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EGFR Mutation Is Associated with Short Progression-Free Survival in Patients with Stage III Non-squamous Cell Lung Cancer Treated with Concurrent Chemoradiotherapy: Song Ee Park, Jae Myoung Noh, You Jin Kim, Han Sang Lee, Jang Ho Cho, Sung Won Lim, Yong Chan Ahn, Hongryull Pyo, Yoon-La Choi, Joungho Han, Jong-Mu Sun, Se Hoon Lee, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn; Cancer Res Treat. 2019;51(2):493-501. Published online June 18, 2018; DOI: https://doi.org/10.4143/crt.2018.125

Abstract PDF PubReader ePub

Purpose
This study was conducted to evaluate the relationship between epidermal growth factor receptor (EGFR) mutation and clinical outcomes in patients with stage III non-squamous cell lung cancer treated with definitive concurrent chemoradiotherapy (CCRT).
Materials and Methods
From January 2008 to December 2013, the medical records of 197 patients with stage III non- squamous non-small cell lung cancer treated with definitive CCRT were analyzed to determine progression-free survival (PFS) and overall survival (OS) according to EGFR mutation status.
Results
Among 197 eligible patients, 81 patients were EGFR wild type, 36 patients had an EGFR mutation (exon 19 Del, n=18; L858R, n=9, uncommon [G719X, L868, T790M], n=9), and 80 patients had unknown EGFR status. The median age was 59 years (range, 28 to 80 years) and 136 patients (69.0%) were male. The median follow-up duration was 66.5 months (range, 1.9 to 114.5 months). One hundred sixty-four patients (83.2%) experienced disease progression. Median PFS was 8.9 months for the EGFR mutation group, 11.8 months for EGFR wild type, and 10.5 months for the unknown EGFR group (p=0.013 and p=0.042, respectively). The most common site of metastasis in the EGFR mutant group was the brain. However, there was no significant difference in OS among the three groups (34.6 months for EGFR mutant group vs. 31.9 months for EGFR wild type vs. 22.6 months for EGFR unknown group; p=0.792 and p=0.284). A total of 29 patients (80.6%) with EGFR mutation were treated with EGFR tyrosine kinase inhibitor (gefitinib, n=24; erlotinib, n=3; afatinib, n=2) upon progression.
Conclusion
EGFR mutation is associatedwith short PFS and the brain is the most common site of distant metastasis in patients with stage III non- squamous cell lung cancer treated with CCRT.

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Role of Adjuvant Thoracic Radiation Therapy and Full Dose Chemotherapy in pN2 Non-small Cell Lung Cancer: Elucidation Based on Single Institute Experience: Hyojung Park, Dongryul Oh, Yong Chan Ahn, Hongryull Pyo, Jae Myung Noh, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Keunchil Park, Hong Kwan Kim, Yong Soo Choi, Jhingook Kim, Jae Ill Zo, Young Mog Shim; Cancer Res Treat. 2017;49(4):880-889. Published online December 12, 2016; DOI: https://doi.org/10.4143/crt.2016.442

Abstract PDF PubReader ePub

Purpose
The optimal adjuvant therapy modality for treating pN2 non-small cell lung cancer patients has not yet been established. In this study, the authors investigated clinical outcomes following three different adjuvant therapy modalities.
Materials and Methods
From January 2006 to December 2012, 240 patients with cN0/1 disease were found to have pN2 disease following curative resection and received one of three adjuvant therapy modalities:thoracic radiation therapy (TRT) and concurrent chemotherapy (CTx) (CCRT) (group I), CCRT plus consolidation CTx (group II), and CTx alone (group III). TRT was delivered to 155 patients (groups I/II), and full dose CTxwas delivered to 172 patients either as a consolidative or a sole modality (group II/III).
Results
During 30 months of median follow-up, 44 patients died and 141 developed recurrence. The 5-year overall survival (OS), locoregional control (LRC), distant metastasis-free survival (DMFS), and disease-free survival (DFS) rates of all patients were 76.2%, 80.7%, 36.4%, and 29.6%, respectively. There was no difference in OS among groups. TRT (groups I/II) significantly improved LRC, full dose CTx (groups II/III) did DMFS, and CCRT plus consolidation CTx (group II) did DFS, respectively.
Conclusion
The current study could support that TRT could improve LRC and full dose CTx could improve DMFS and that CCRT plus consolidation CTx could improve DFS.

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The effect of adjuvant chemoradiotherapy on survival after R0 resection for stage III-N2 nonsmall cell lung cancer: A meta-analysis
Dailong Li, Wanqiang Li, Yaqi Pang, Lu Xu, Xinhua Xu
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The efficacy of postoperative radiotherapy for patients with non-small cell lung cancer
Zexu Wang, Baixia Yang, Ping Zhan, Li Wang, Bing Wan
Journal of Cancer Research and Therapeutics.2022; 18(7): 1910. CrossRef

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Radiation Therapy Alone in cT1-3N0 Non-small Cell Lung Cancer Patients Who Are Unfit for Surgical Resection or Stereotactic Radiation Therapy: Comparison of Risk-Adaptive Dose Schedules: Won Kyung Cho, Jae Myoung Noh, Yong Chan Ahn, Dongryul Oh, Hongryull Pyo; Cancer Res Treat. 2016;48(4):1187-1195. Published online March 9, 2016; DOI: https://doi.org/10.4143/crt.2015.391

Abstract PDF PubReader ePub

Purpose
High dose definitive radiation therapy (RT) alone is recommended to patients with cT1-3N0 non-small cell lung cancer, who are unfit for surgery or stereotactic RT. This study was conducted to evaluate the clinical outcomes and cost-effectiveness following RT alone using two different modest hypofractionation dose schemes. Materials and Methods Between 2001 and 2014, 124 patients underwent RT alone. From 2001 till 2010, 60 Gy in 20 fractions was delivered to 79 patients (group 1). Since 2011, 60 Gy in 20 fractions (group 2, 20 patients), and 60 Gy in 15 fractions (group 3, 25 patients) were selectively chosen depending on estimated risk of esophagitis.
Results
At follow-up of 16.7 months, 2-year rates of local control, progression-free survival, and overall survival were 62.6%, 39.1%, and 59.1%, respectively. Overall survival was significantly better in group 3 (p=0.002). In multivariate analyses, cT3 was the most powerful adverse factor affecting clinical outcomes. Incidence and severity of radiation pneumonitis were not different among groups, while no patients developed grade 2 esophagitis in group 3 (p=0.003). Under current Korean Health Insurance Policy, RT cost per person was 22.5% less in group 3 compared with others. Conclusion The current study demonstrated that 60 Gy in 15 fractions instead of 60 Gy in 20 fractions resulted in comparable clinical outcomes with excellent safety, direct cost saving, and improved convenience to the patients with tumors located at ≥ 1.5 cm from the esophagus.

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Kyungmi Yang, Jae Myoung Noh, Yeon Jeong Kim, Hongryull Pyo
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Kyungmi Yang, Jae Myoung Noh, Hye Yun Park, Hongseok Yoo, Sun Hye Shin, Hongryull Pyo
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Definitive Bimodality Concurrent Chemoradiotherapy in Patients with Inoperable N2-positive Stage IIIA Non-small Cell Lung Cancer: Jae Myoung Noh, Yong Chan Ahn, Hyebin Lee, Hongryull Pyo, BoKyong Kim, Dongryul Oh, Hyojung Park, Eonju Lee, Keunchil Park, Jin Seok Ahn, Myung-Ju Ahn, Jong-Mu Sun; Cancer Res Treat. 2015;47(4):645-652. Published online February 12, 2015; DOI: https://doi.org/10.4143/crt.2014.144

Abstract PDF PubReader ePub

Purpose
This study was conducted to evaluate the treatment outcomes following definitive bimodality concurrent chemoradiotherapy (CCRT) in patients with inoperable N2-positive stage IIIA (N2- IIIA) non-small cell lung cancer (NSCLC). Materials and Methods From May 1997 to December 2012, 65 out of 633 patients with N2-IIIA NSCLC received bimodality therapy. The treatment modality was selected during/after neoadjuvant CCRT in 21 patients or primarily at diagnosis in 44 through a multidisciplinary consensus meeting. The median age was 65 years (range, 36 to 76 years). Sixty patients (92.3%) had clinically evident N2 disease, while 22 (33.8%) had multi-station N2 involvement. The median radiation therapy dose was 66 Gy in 33 fractions, while the dose was elevated to 72 Gy in 13 patients who had a treatment break due to delayed decision regarding resectability. The most frequent chemotherapy regimen was weekly paclitaxel or docetaxel plus cisplatin or carboplatin (54, 83.1%).
Results
During the median follow-up of 18.8 months (range, 1.6 to 173.1 months), 34 patients (52.3%) experienced disease progression, with distant metastasis being the most common first treatment failure pattern (23, 34.8%). The median and 2-year rates of progression-free survival were 18.8 months and 45.9%, respectively. The median and 2-year rates of overall survival were 28.6 months and 50.1%, respectively. Conclusion Definitive bimodality therapy in patients with N2-IIIA NSCLC demonstrated favorable outcomes, while trimodality therapy could be considered for candidates for less than pneumonectomy.

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Effect of Radiation Therapy Techniques on Outcome in N3-positive IIIB Non-small Cell Lung Cancer Treated with Concurrent Chemoradiotherapy: Jae Myoung Noh, Jin Man Kim, Yong Chan Ahn, Hongryull Pyo, BoKyong Kim, Dongryul Oh, Sang Gyu Ju, Jin Sung Kim, Jung Suk Shin, Chae-Seon Hong, Hyojung Park, Eonju Lee; Cancer Res Treat. 2016;48(1):106-114. Published online February 12, 2015; DOI: https://doi.org/10.4143/crt.2014.131

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Purpose
This study was conducted to evaluate clinical outcomes following definitive concurrent chemoradiotherapy (CCRT) for patients with N3-positive stage IIIB (N3-IIIB) non-small cell lung cancer (NSCLC), with a focus on radiation therapy (RT) techniques. Materials and Methods From May 2010 to November 2012, 77 patients with N3-IIIB NSCLC received definitive CCRT (median, 66 Gy). RT techniques were selected individually based on estimated lung toxicity, with 3-dimensional conformal RT (3D-CRT) and intensity-modulated RT (IMRT) delivered to 48 (62.3%) and 29 (37.7%) patients, respectively. Weekly docetaxel/paclitaxel plus cisplatin (67, 87.0%) was the most common concurrent chemotherapy regimen.
Results
The median age and clinical target volume (CTV) were 60 years and 288.0 cm3, respectively. Patients receiving IMRT had greater disease extent in terms of supraclavicular lymph node (SCN) involvement and CTV ≥ 300 cm3. The median follow-up time was 21.7 months. Fortyfive patients (58.4%) experienced disease progression, most frequently distant metastasis (39, 50.6%). In-field locoregional control, progression-free survival (PFS), and overall survival (OS) rates at 2 years were 87.9%, 38.7%, and 75.2%, respectively. Although locoregional control was similar between RT techniques, patients receiving IMRT had worse PFS and OS, and SCN metastases from the lower lobe primary tumor and CTV ≥ 300 cm3were associated with worse OS. The incidence and severity of toxicities did not differ significantly between RT techniques. Conclusion IMRT could lead to similar locoregional control and toxicity, while encompassing a greater disease extent than 3D-CRT. The decision to apply IMRT should be made carefully after considering oncologic outcomes associated with greater disease extent and cost.

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