Cancer Research and Treatment

Original Articles

Clinical Impact of TP53 Mutations in Patients with Head and Neck Cancer Who Were Treated with Targeted Therapies or Immunotherapy: Eun Joo Kang, Shinwon Hwang, Yun-Gyoo Lee, Jong-Kwon Choi, Seong Hoon Shin, Yoon Hee Choi, Keun-Wook Lee, Hyun Woo Lee, Min Kyoung Kim, Seung Taek Lim, Hwan Jung Yun, Sang-Gon Park, Sangwoo Kim, Sung-Bae Kim, Hye Ryun Kim; Received August 28, 2024 Accepted December 21, 2024 Published online December 23, 2024; DOI: https://doi.org/10.4143/crt.2024.836 [Accepted]

Abstract PDF: Purpose
TP53 mutations are common in head and neck squamous cell carcinoma (HNSCC). We evaluated their clinical impact in patients treated with targeted agents or immunotherapy in the KCSG HN15-16 TRIUMPH trial.
Materials and Methods
We analyzed clinical characteristics and outcomes of patients with TP53 mutations in the TRIUMPH trial, a multicenter, biomarker-driven umbrella trial in Korea. Patients were assigned to treatment groups based on genomic profiles: Group 1, alpelisib; Group 2, poziotinib; Group 3, nintedanib; and Group 4, abemaciclib. If there was no identifiable target, the patients were allocated to Group 5 (durvalumab ± tremelimumab).
Results
TP53 mutations were detected in 116/179 patients (64.8%), more frequently in HPV-negative and non-oropharyngeal cancers. Patients with TP53 mutations exhibited shorter progression-free survival (PFS) than TP53 wild-type in all the patients (1.7 vs. 3.8 months, p=0.002) and in those who received targeted treatments (2.5 vs. 7.3 months, p=0.009). Furthermore, TP53 mutations were strongly associated with poor overall survival than TP53 wild-type in all the patients (11.1 vs. 28.8 months, p=0.005) and in Group 5 (8.1 vs. 33.0 months, p=0.001).
Conclusion
TP53 mutations were associated with aggressive clinical characteristics and poor survival, particularly in HNSCC patients treated with immunotherapy.

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Target-Enhanced Whole-Genome Sequencing Shows Clinical Validity Equivalent to Commercially Available Targeted Oncology Panel: Sangmoon Lee, Jin Roh, Jun Sung Park, Islam Oguz Tuncay, Wonchul Lee, Jung-Ah Kim, Brian Baek-Lok Oh, Jong-Yeon Shin, Jeong Seok Lee, Young Seok Ju, Ryul Kim, Seongyeol Park, Jaemo Koo, Hansol Park, Joonoh Lim, Erin Connolly-Strong, Tae-Hwan Kim, Yong Won Choi, Mi Sun Ahn, Hyun Woo Lee, Seokhwi Kim, Jang-Hee Kim, Minsuk Kwon; Received February 3, 2024 Accepted September 12, 2024 Published online September 19, 2024; DOI: https://doi.org/10.4143/crt.2024.114 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS.
Materials and Methods
This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches.
Results
TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making.
Conclusion
TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

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Head and Neck cancer

A Phase II Trial of Nintedanib in Patients with Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma: In-Depth Analysis of Nintedanib Arm from the KCSG HN 15-16 TRIUMPH Trial: Kyoo Hyun Kim, Sun Min Lim, Hee Kyung Ahn, Yun-Gyoo Lee, Keun-Wook Lee, Myung-Ju Ahn, Bhumsuk Keam, Hye Ryun Kim, Hyun Woo Lee, Ho Jung An, Jin-Soo Kim; Cancer Res Treat. 2024;56(1):37-47. Published online July 20, 2023; DOI: https://doi.org/10.4143/crt.2023.433

Abstract PDF PubReader ePub

Purpose
Precision oncology approach for recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) is necessary due to its dismal prognosis. We performed a genomic profile-based umbrella trial of patients with platinum-refractory HNSCC (KCSG-TRIUMPH). Here, we present an in-depth report of the the nintedanib arm (arm 3) of the current trial.
Materials and Methods
The TRIUMPH study was a multicenter, open-label, single-arm phase 2 trial, in which patients were assigned to treatment arms based on next-generation sequencing (NGS)–based, matching genomic profiles. Patients whose tumors harbor fibroblast growth factor receptor (FGFR) alteration were enrolled in the nintedanib arm (arm 3) as part of the TRIUMPH study. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), safety, and biomarker analysis.
Results
Between October 2017 and August 2020, 207 were enrolled in the TRIUMPH study, and eight were enrolled in the nintedanib arm. ORR and disease control rate were 42.9% and 57.1%, respectively. The median PFS was 5.6 months and the median duration of response was 9.1 months. Median OS was 11.1 months. One patient maintained the partial response for 36 months. Overall, the toxicity profiles were manageable.
Conclusion
Single-agent nintedanib has demonstrated significant efficacy in FGFR-mutated, recurrent or metastatic HNSCC patients, with tolerable toxicity profiles. The results from the study have provided the basis for routine NGS screening and FGFR-targeted therapy. Because of the small number of patients due to slow accrual in this study, further studies with a larger cohort are warranted for statistical power.

Citations

Citations to this article as recorded by

One-pot synthesis and pharmacological evaluation of new quinoline/pyrimido-diazepines as pulmonary antifibrotic agents
Michael Atef Fawzy, Karim Hagag Ibrahim, Ashraf A Aly, Asmaa H Mohamed, Sara Mohamed Naguib Abdel Hafez, Walaa Yehia Abdelzaher, Eslam B Elkaeed, Aisha A Alsfouk, El-Shimaa MN Abdelhafez
Future Medicinal Chemistry.2024; 16(21): 2211. CrossRef
Critical review of the current and future prospects of VEGF-TKIs in the management of squamous cell carcinoma of head and neck
Prashant Puttagunta, Saagar V. Pamulapati, James E. Bates, Jennifer H. Gross, William A. Stokes, Nicole C. Schmitt, Conor Steuer, Yong Teng, Nabil F. Saba
Frontiers in Oncology.2023;[Epub] CrossRef

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Lung and Thoracic cancer

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

Abstract PDF Supplementary Material PubReader ePub

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

Citations to this article as recorded by

Lung Cancer in Women: The Past, Present, and Future
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Lung cancer screening for never smokers: current evidence and future directions
Kay Choong See
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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
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Health risk assessment for particulate matter: application of AirQ+ model in the northern Caribbean region of Colombia
Heli A. Arregocés, Roberto Rojano, Gloria Restrepo
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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
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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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Investigating the Feasibility of Targeted Next-Generation Sequencing to Guide the Treatment of Head and Neck Squamous Cell Carcinoma: Sun Min Lim, Sang Hee Cho, In Gyu Hwang, Jae Woo Choi, Hyun Chang, Myung-Ju Ahn, Keon Uk Park, Ji-Won Kim, Yoon Ho Ko, Hee Kyung Ahn, Byoung Chul Cho, Byung-Ho Nam, Sang Hoon Chun, Ji Hyung Hong, Jung Hye Kwon, Jong Gwon Choi, Eun Joo Kang, Tak Yun, Keun-Wook Lee, Joo-Hang Kim, Jin Soo Kim, Hyun Woo Lee, Min Kyoung Kim, Dongmin Jung, Ji Eun Kim, Bhumsuk Keam, Hwan Jung Yun, Sangwoo Kim, Hye Ryun Kim; Cancer Res Treat. 2019;51(1):300-312. Published online May 9, 2018; DOI: https://doi.org/10.4143/crt.2018.012

Abstract PDF Supplementary Material PubReader ePub

Purpose
Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients.
Materials and Methods
Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data.
Results
Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)–negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%).
Conclusion
We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.

Citations

Citations to this article as recorded by

Personalized Biomarker-Based Umbrella Trial for Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: KCSG HN 15-16 TRIUMPH Trial
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Journal of Clinical Oncology.2024; 42(5): 507. CrossRef
A Phase II Trial of Nintedanib in Patients with Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma: In-Depth Analysis of Nintedanib Arm from the KCSG HN 15-16 TRIUMPH Trial
Kyoo Hyun Kim, Sun Min Lim, Hee Kyung Ahn, Yun-Gyoo Lee, Keun-Wook Lee, Myung-Ju Ahn, Bhumsuk Keam, Hye Ryun Kim, Hyun Woo Lee, Ho Jung An, Jin-Soo Kim
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Mutationssignaturen beim Kopf- und Hals-Tumor
M. Plath, J. Hess, K. Zaoui
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BAMixChecker: an automated checkup tool for matched sample pairs in NGS cohort
Hein Chun, Sangwoo Kim, Inanc Birol
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A Review of HPV-Related Head and Neck Cancer
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Patient’s Cognitive Function and Attitudes towards Family Involvement in Cancer Treatment Decision Making: A Patient-Family Caregiver Dyadic Analysis: Dong Wook Shin, Juhee Cho, Debra L. Roter, So Young Kim, Jong Hyock Park, Hyung Kook Yang, Hyun Woo Lee, Sun-Seog Kweon, Yune Sik Kang, Keeho Park; Cancer Res Treat. 2018;50(3):681-690. Published online July 4, 2017; DOI: https://doi.org/10.4143/crt.2017.201

Abstract PDF PubReader ePub

Purpose
Older patient populations commonly have cognitive impairment, which might impact decisional capacity. We examined patients and family caregivers preferences for family involvement in treatment decision making assuming different level of cognitive impairment, and sought to explore the factors associated with the preferences and the degree to which patients and family members agree on preferences.
Materials and Methods
A total of 358 elderly cancer patient and caregiver dyads were recruited from the 11 cancer centers in Korea andwere asked to express their preferences forfamily involvement in treatment decision making using hypothetical scenarios with three different levels of cognitive status (intact, mild impairment, and severe impairment).
Results
Both patients and family caregivers preferred greater family dominance in treatment decision makingwith the increasing the level of cognitive impairment (39.7%, 60.9%, and 86.6% for patients and 45.0%, 66.2%, and 89.7% for caregivers in each scenarios). Patient and family caregiver concordance in decisional control preference was small for all three scenarios (weighted κ=0.32, κ=0.26, and κ=0.36, respectively). Higher patient education was associated with preference for patient dominance in treatment decision in conditions of both mild and severe cognitive impairment. The association of higher patient education and patient-caregiver preference concordance was positive with intact cognition, while it was negative with severe cognitive impairment.
Conclusion
Decision control preferences were affected by hypothesized cognitive status of the patients. Findings from our study would be helpful to develop effective strategy for optimizing family involvement in cancer treatment decision in the context of deteriorating cognitive function of the patients.

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Abstract PDF: In order to assess the efficacy of alternating schedule chemotherapy on the outcome of patients with small cell lung cancer and effect of concurrent thoracic radiotherapy in limited disease, fifty five eligible patients with SCLC were treated with chemotherapy consisting of cyclophosphamide, adriamycin and vincristine(CAV) alternating with etoposide and cisplatin(EP). Thoracic radiotherapy was administered to the patients with limited stage disease Overall response rate was 64% with 20% of complete response. The response rate was 78%(CR 39%,PR 39%)in the patients with limited stage disease, and 53%(CR 6%, PR 47%)in those with extensive stage disease. With median follow-up period of 14 months (341+), the median survivals in patients of limited stage and extended disease were 15 months and 10 month, respectively (p<0.02) and median survivals in patients with CR, PR, and SD+PD were 20, 11.3, 8.5months, respectively(p<0.01) In patients with limited stage patients with or without concurrent use of thoracic radiotherapy, the response rates were 82%(CR 42%, PR 41%) and 67%(CR 33%, PR 34%) and median survivals were 15.8 months and 11.8 months, respectively.There were no life threatening side effects. This results suggest that alternating chemotherapy with CAV and EP may be useful as a treatement strategy in small cell lung cancer and concurrent use of thoracic radiotherapy in limited stage patients improve survival, but it was not significant statistically.

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