Cancer Research and Treatment

Original Articles

Lung and Thoracic cancer

A Randomized Phase II Study of Irinotecan Plus Cisplatin with or without Simvastatin in Ever-Smokers with Extended Disease Small Cell Lung Cancer: Youngjoo Lee, Soo-Hyun Lee, Geon Kook Lee, Eun Jin Lim, Ji-Youn Han; Cancer Res Treat. 2023;55(3):885-893. Published online March 20, 2023; DOI: https://doi.org/10.4143/crt.2023.283

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Purpose
This study evaluated whether an addition of simvastatin to chemotherapy improves survival in ever-smokers with extensive disease (ED)–small cell lung cancer (SCLC).
Materials and Methods
This is an open-label randomized phase II study conducted in National Cancer Center (Goyang, Korea). Chemonaive patients with ED-SCLC, smoking history (≥ 100 cigarettes lifetime), and Eastern Cooperative Oncology Group performance status of ≤ 2 were eligible. Patients were randomized to receive irinotecan plus cisplatin alone or with simvastatin (40 mg once daily orally) for a maximum of six cycles. Primary endpoint was the the 1-year survival rate.
Results
Between September 16, 2011, and September 9, 2021, 125 patients were randomly assigned to the simvastatin (n=62) or control (n=63) groups. The median smoking pack year was 40 years. There was no significant difference in the 1-year survival rate between the simvastatin and control groups (53.2% vs. 58.7%, p=0.535). The median progression-free survival and overall survival between the simvastatin arm vs. the control groups were 6.3 months vs. 6.4 months (p=0.686), and 14.4 months vs. 15.2 months, respectively (p=0.749). The incidence of grade 3-4 adverse events was 62.9% in the simvastatin group and 61.9% in the control group. In the exploratory analysis of lipid profiles, patients with hypertriglyceridemia had significantly higher 1-year survival rates than those with normal triglyceride levels (80.0% vs. 52.7%, p=0.046).
Conclusion
Addition of simvastatin to chemotherapy provided no survival benefit in ever-smokers with ED-SCLC. Hypertriglyceridemia may be associated with better prognosis in these patient population.

Citations

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Cardiovascular/anti‐inflammatory drugs repurposed for treating or preventing cancer: A systematic review and meta‐analysis of randomized trials
David J. Benjamin, Alyson Haslam, Vinay Prasad
Cancer Medicine.2024;[Epub] CrossRef
Repurposing simvastatin in cancer treatment: an updated review on pharmacological and nanotechnological aspects
Nargis Ara, Abdul Hafeez, Shom Prakash Kushwaha
Naunyn-Schmiedeberg's Archives of Pharmacology.2024; 397(10): 7377. CrossRef
Strategies to Target Chemoradiotherapy Resistance in Small Cell Lung Cancer
Tony Yu, Benjamin H. Lok
Cancers.2024; 16(20): 3438. CrossRef
β-blockers and statins: exploring the potential off-label applications in breast, colorectal, prostate, and lung cancers
Pedro Gabriel Senger Braga, Janaína da Silva Vieira, Aline Rachel Bezerra Gurgel, Patricia Chakur Brum
Frontiers in Pharmacology.2024;[Epub] CrossRef
Statins—From Fungi to Pharmacy
Anna Sadowska, Patryk Osiński, Alicja Roztocka, Karolina Kaczmarz-Chojnacka, Ewa Zapora, Diana Sawicka, Halina Car
International Journal of Molecular Sciences.2023; 25(1): 466. CrossRef

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Long-term Exposure to PM₁₀ Increases Lung Cancer Risks: A Cohort Analysis: Hyun Woo Lee, Sung-Chan Kang, Sun-Young Kim, Young-Jae Cho, Seungsik Hwang; Cancer Res Treat. 2022;54(4):1030-1037. Published online January 17, 2022; DOI: https://doi.org/10.4143/crt.2021.1030

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Purpose
Although lung cancer incidences in female never-smokers have increased, few studies focus on explicit investigation. We aimed to investigate the relationship between long-term exposure to ambient particulate matter sized 10 μm or less in diameter (PM₁₀) and the incidence of lung cancer within different genders and smoking status populations.
Materials and Methods
We included Seoul metropolitan residents, aged between 20 and 65 years, who underwent a national health screening examination from 2005-2007 and were followed up until 2015. Individual-level long-term exposure to PM₁₀ was assessed based on subject home addresses. To assess the relationship between PM₁₀ and lung cancer, we estimated hazard ratios (HRs) for increased lung cancer incidence from a 10 µg/m³ increase in PM₁₀.
Results
Among 5,831,039 individuals, 36,225 (0.6%) developed lung cancer within the 7 years observed. In females, the majority (94.4%) of lung cancer development was found in never-smokers. In adjusted analyses, a significant relationship between lung cancer development and PM₁₀ was observed in males, regardless of smoking status (never-smoker: HR, 1.14 [95% confidence interval (CI), 1.13 to 1.15]; ex-smoker: HR, 1.16 [95% CI, 1.14 to 1.17]; current smoker: HR, 1.18 [95% CI, 1.17 to 1.19]). We also found significant associations in female never- or ex-smokers with smaller HRs (never-smoker: HR, 1.06 [95% CI, 1.05 to 1.07]; ex-smoker: HR, 1.13 [95% CI, 1.02 to 1.23]; current smoker: HR, 1.04 [95% CI, 0.99 to 1.10]).
Conclusion
Our findings suggest that long-term exposure to PM₁₀ is associated with lung cancer development. A novel approach to lung cancer screening needs to be considered depending on the exposed PM₁₀ level.

Citations

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Physics-informed calibration model for enhanced accuracy in particulate matter monitoring integrating clustering algorithms with field validation
Zikang Feng, Lina Zheng, Ning Xue
Expert Systems with Applications.2025; 277: 127313. CrossRef
Lung Cancer in Women: The Past, Present, and Future
Narjust Florez, Lauren Kiel, Ivy Riano, Shruti Patel, Kathryn DeCarli, Natasha Dhawan, Ivy Franco, Ashley Odai-Afotey, Kelly Meza, Nishwant Swami, Jyoti Patel, Lecia V. Sequist
Clinical Lung Cancer.2024; 25(1): 1. CrossRef
Impact of air pollution on cardiorespiratory morbidities in Southern Thailand
Suhaimee Buya, Apiradee Lim, Rattikan Saelim, Salang Musikasuwan, Thitiworn Choosong, Nutta Taneepanichskul
Clinical Epidemiology and Global Health.2024; 25: 101501. CrossRef
Lung cancer screening for never smokers: current evidence and future directions
Kay Choong See
Singapore Medical Journal.2024;[Epub] CrossRef
Airborne particulate matter integral assessment in Magdalena department, Colombia: Patterns, health impact, and policy management
Eliana Vergara-Vásquez, Luis M. Hernández Beleño, Tailin T. Castrillo-Borja, Tomás R. Bolaño-Ortíz, Yiniva Camargo-Caicedo, Andrés M. Vélez-Pereira
Heliyon.2024; 10(16): e36284. CrossRef
Impact of Global Warming on Cancer Development: A Review of Environmental Carcinogens and Human Immunogenetics
Pardis Shirkani, Afshin Shirkani
West Kazakhstan Medical Journal.2024; 66(3): 210. CrossRef
Health risk assessment for particulate matter: application of AirQ+ model in the northern Caribbean region of Colombia
Heli A. Arregocés, Roberto Rojano, Gloria Restrepo
Air Quality, Atmosphere & Health.2023; 16(5): 897. CrossRef
The dysfunctionality of hippocampal synapses may be directly related to PM-induced impairments in spatial learning and memory in juvenile rats
Jianxiong Gui, Jie Liu, Ziyao Han, Xiaoyue Yang, Ran Ding, Jiaxin Yang, Hanyu Luo, Dishu Huang, Hengsheng Chen, Li Cheng, Li Jiang
Ecotoxicology and Environmental Safety.2023; 254: 114729. CrossRef
Environmental Air Pollutants Affecting Skin Functions with Systemic Implications
Georgeta Bocheva, Radomir M. Slominski, Andrzej T. Slominski
International Journal of Molecular Sciences.2023; 24(13): 10502. CrossRef
Association of Air Pollution with the Number of Common Respiratory Visits in Children in a Heavily Polluted Central City, China
Dan Wang, Yanan Wang, Qianqian Liu, Wenxin Sun, Liangkui Wei, Chengxin Ye, Rencheng Zhu
Toxics.2023; 11(10): 815. CrossRef
Air Pollution and Lung Cancer: Contributions of Extracellular Vesicles as Pathogenic Mechanisms and Clinical Utility
Jonathan González-Ruíz, Andrea A.Baccarelli, David Cantu-de-Leon, Diddier Prada
Current Environmental Health Reports.2023; 10(4): 478. CrossRef
Long-Term Exposure to Air Pollution Associates the Risk of Benign Brain Tumor: A Nationwide, Population-Based, Cohort Study in Taiwan
Kuang-Hsi Chang, Chieh-Lin Jerry Teng, Yi-Chao Hsu, Stella Chin-Shaw Tsai, Han-Jie Lin, Tsai-Ling Hsieh, Chih-Hsin Muo, Chung Y. Hsu, Ruey-Hwang Chou
Toxics.2022; 10(4): 176. CrossRef

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Report of the Korean Association of Lung Cancer Registry (KALC-R), 2014: Chang-Min Choi, Ho Cheol Kim, Chi Young Jung, Deog Gon Cho, Jae Hyun Jeon, Jeong Eun Lee, Jin Seok Ahn, Seung Joon Kim, Yeongdae Kim, Yoo-Duk Choi, Yang-Gun Suh, Jung-Eun Kim, Boram Lee, Young-Joo Won, Young-Chul Kim; Cancer Res Treat. 2019;51(4):1400-1410. Published online February 25, 2019; DOI: https://doi.org/10.4143/crt.2018.704

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Purpose
The aim of this study was to investigate epidemiology, clinical characteristics and sex differences of patients with lung cancer using nationwide registry in Korea.
Materials and Methods
The Korean Association for Lung Cancer developed a registry in cooperation with the Korean Central Cancer Registry, and surveyed about 10% of lung cancer cases. For this first survey of cases diagnosed in 2014, cases were selected through a systematic sampling method.
Results
Total 2,621 lung cancer patients were surveyed, and the median patient age was 70 years. During the study period, adenocarcinoma was the most frequent histologic type, the proportion of female patients was 28.4%, and women had a better prognosis (median survival, not reached vs. 13 months; p<0.001) than did men for non-small cell lung cancer. The proportion of never-smokers was 36.4%, and never-smoking was more prevalent in women than in men (87.5 vs. 16.0%, p<0.001). Epidermal growth factor receptor (EGFR) mutations were found in 36.8% of stage IV adenocarcinoma patients, and higher in female compared to male patients (51.2 vs. 26.6%, p<0.001). In addition, patients with EGFR mutation showed better survival (median survival, 18 vs. 8 months; p<0.001) than patients without EGFR mutation in these patients.
Conclusion
This is the first survey to gather unbiased nationwide lung cancer statistics in Korea. More than one-third of lung cancer patients had no smoking history. Female had a high proportion of non-smoker, more adenocarcinoma with EGFR mutation and generally better prognosis than male.

Citations

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E. Giroux Leprieur, A. Vergnenègre, J. Trédaniel
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12,899 View
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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

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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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Lung Cancer Screening with Low-Dose CT in Female Never Smokers: Retrospective Cohort Study with Long-term National Data Follow-up: Hyae Young Kim, Kyu-Won Jung, Kun Young Lim, Soo-Hyun Lee, Jae Kwan Jun, Jeongseon Kim, Bin Hwangbo, Jin Soo Lee; Cancer Res Treat. 2018;50(3):748-756. Published online July 17, 2017; DOI: https://doi.org/10.4143/crt.2017.312

Abstract PDF Supplementary Material PubReader ePub

Purpose
Because of growing concerns about lung cancer in female never smokers, chest low-dose computed tomography (LDCT) screening is often performed although it has never shown clinical benefits. We examinewhether or not female never smokers really need annual LDCT screening when the initial LDCT showed negative findings.
Materials and Methods
This retrospective cohort study included 4,365 female never smokers aged 40 to 79 years who performed initial LDCT from Aug 2002 to Dec 2007. Lung cancer diagnosis was identified from the Korea Central Cancer Registry Database registered until December 31, 2013. We calculated the incidence, cumulative probability, and standardized incidence ratio (SIR) of lung cancer by Lung Imaging Reporting and Data System (Lung-RADS) categories showed on initial LDCT.
Results
After median follow-up of 9.69 years, 22 (0.5%) had lung cancer. Lung cancer incidence for Lung-RADS category 4 was 1,848.4 (95% confidence interval [CI], 1,132.4 to 3,017.2) per 100,000 person-years and 16.4 (95% CI, 7.4 to 36.4) for categories 1, 2, and 3 combined. The cumulative probability of lung cancer for category 4 was 10.6% at 5 years and 14.8% at 10 years while they were 0.07% and 0.17% when categories 1, 2, and 3 were combined. The SIR for subjects with category 4 was 43.80 (95% CI, 25.03 to 71.14), which was much higher than 0.47 (95% CI, 0.17 to 1.02) for categories 1, 2, and 3 combined.
Conclusion
Considering the low risk of lung cancer development in female never smokers, it seems unnecessary to repeat annual LDCT screening for at least 5 years or even longer unless the initial LDCT showed Lung-RADS category 4 findings.

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