Cancer Research and Treatment

Original Articles

Pilot Study for Feasibility of Onco-Geriatric Intervention Model in Older Patients with Cancer in a Tertiary Academic Hospital: Jin Won Kim, Jung-Yeon Choi, Woochan Park, Minsu Kang, Jeongmin Seo, Eun Hee Jung, Koung Jin Suh, Ji-Won Kim, Se Hyun Kim, Yu Jung Kim, Keun-Wook Lee, Sang-A Kim, Ji Yun Lee, Jeong-Ok Lee, Soo-Mee Bang, Kwang-il Kim, Jee Hyun Kim; Received January 20, 2025 Accepted March 11, 2025 Published online March 12, 2025; DOI: https://doi.org/10.4143/crt.2025.079 [Accepted]

Abstract PDF: Purpose
Older cancer patients face unique challenges due to age-related physiological changes, increasing their vulnerability to treatment-related toxicities. Geriatric assessment (GA) is a validated tool for optimizing care, yet there is no consensus on integrating geriatric interventions into oncology. This study evaluates the feasibility of a tailored onco-geriatric intervention model incorporating the KG-7 screening tool.
Materials and Methods
This prospective study included 30 patients aged ≥70 years with solid tumors undergoing adjuvant or palliative chemotherapy. Patients scoring ≤5 of KG-7 were eligible. Tailored interventions incorporating KG-7 included polypharmacy, functional status, mobility, nutrition, cognition, emotional well-being, insomnia, social support, and medical problem. KG-7, GA, and quality of life (QoL) were followed at 12 weeks.
Results
Participants (median age: 79.5 years) had colon (43.3%), pancreatic (23.3%), or gastric cancer (23.3%). At baseline, most patients showed independent ADL (100%)/IALD (90%). However, 93.3% had abnormal GA. Particularly, 86.7% were either malnourished or at risk of malnutrition. The most frequently identified intervention needs included polypharmacy (70.0%), nutritional support (60.0%), and emotional well-being (50.0%) with high adherence (100.0%, 88.9%, and 46.7%, respectively). At 12 weeks, KG-7 scores improved in 43.8% of patients, and 69.2% of GA domains were improved. QoL analysis revealed modest improvement in Global Health Status (mean difference 6.3, p=0.176). One-year survival rates were 92.3% and 79.4% for adjuvant and palliative groups, respectively.
Conclusion
The onco-geriatric intervention model incorporating KG-7 demonstrated high feasibility and potential to enhance clinical outcomes. Future studies should validate this approach in randomized trials to optimize care for older cancer patients.

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Differential Efficacy of Alpelisib by PIK3CA Mutation Site in Head and Neck Squamous Cell Carcinoma: An Analysis from the KCSG HN 15-16 TRIUMPH Trial: Kyoo Hyun Kim, Shinwon Hwang, Min Kyoung Kim, Keon-Uk Park, Tak Yun, Keun-Wook Lee, Joo Hang Kim, Bhumsuk Keam, Byoung Chul Cho, So Yeon Oh, Sang Hee Cho, Sangwoo Kim, Sung-Bae Kim, Min Hee Hong, Hye Ryun Kim; Received December 11, 2024 Accepted January 27, 2025 Published online January 31, 2025; DOI: https://doi.org/10.4143/crt.2024.1195 [Accepted]

Abstract PDF: Purpose
The TRIUMPH trial was a biomarker-driven umbrella trial for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). This analysis focuses on the PIK3CAɑ inhibitor alpelisib (arm 1) in patients with phosphoinositide 3-kinase (PI3K) pathway alterations.
Materials and Methods
Patients with PI3K pathway altered tumors were enrolled in the alpelisib arm of the TRIUMPH study. We conducted a detailed analysis of the correlation between PI3K pathway mutations and treatment outcomes including disease control rate (DCR), overall survival (OS), and progression-free survival (PFS).
Results
From Oct 2017 and Aug 2020, 203 were enrolled, with 42 treated with alpelisib. Response evaluation was possible for 33 patients. Genomic profiles revealed PIK3CA amplifications in 26.2%, and point mutations in E542K (26.2%), E545K (23.8%), and H1047R (9.5%). Neither PIK3CA amplification nor co-occurring TP53 mutations had a notable influence on alpelisib response or survival outcomes. Although the overall response rates were similar between helical domain mutations (E542, E545) and kinase domain mutations (H1047), patients with H1047 mutations exhibited significantly poorer PFS compared to those with non-H1047 PIK3CA alterations (1.6 vs. 7.3 months, p=0.017). OS in patients with H1047 kinase domain mutations showed a trend toward being shorter compared to others, though this difference did not reach statistical significance.
Conclusion
Alpelisib showed differential efficacy based on PI3K pathway alterations in patients with R/M HNSCC and was well-tolerated. These findings suggest the usefulness of NGS testing-based decision-making when using the targeted agents in R/M HNSCC. We need to confirm results in larger cohorts.

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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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The Role of Direct Oral Anticoagulants in Managing Myeloproliferative Neoplasms Patients: Ji Yun Lee, Ju-Hyun Lee, Woochan Park, Jeongmin Seo, Minsu Kang, Eun Hee Jung, Sang-A Kim, Koung Jin Suh, Ji-Won Kim, Se Hyun Kim, Jeong-Ok Lee, Jin Won Kim, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang; Received August 5, 2024 Accepted September 19, 2024 Published online September 20, 2024; DOI: https://doi.org/10.4143/crt.2024.738 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub

Purpose
Thrombosis and bleeding significantly affect morbidity and mortality in myeloproliferative neoplasms (MPNs). The efficacy and safety of direct oral anticoagulants (DOACs) in MPN patients remain uncertain.
Materials and Methods
We conducted a large, retrospective, nationwide cohort study using the Korean Health Insurance Review and Assessment Service database from 2010 to 2021.
Results
Out of the 368 MPN patients included in the final analysis, 62.8% were treated with DOACs for atrial fibrillation (AF), and 37.2% for venous thromboembolism (VTE). The AF group was statistically older with higher CHA2DS2-VASc (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke, transient ischemic attack, or thromboembolism, vascular disease, age 65-74 years, sex category [female]) scores compared to the VTE group. Antiplatelet agents were used in 51.1% of cases, and cytoreductive drugs in 79.3%, with hydroxyurea being the most common (64.9%). The median follow-up was 22.3 months, with 1-year cumulative incidence rates of thrombosis and bleeding at 11.1% and 3.7%, respectively. Multivariate analysis identified CHA2DS2-VASc scores ≥ 3 (hazard ratio [HR], 3.48), concomitant antiplatelet use (HR, 2.57), and cytoreduction (HR, 2.20) as significant thrombosis risk factors but found no significant predictors for major bleeding.
Conclusion
Despite the limitations of retrospective data, DOAC treatment in MPN patients seems effective and has an acceptable bleeding risk.

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Survey of Clinical Practice in Chronic Myeloproliferative Neoplasms in Croatia: A Study by the MPN Working Group Party of the Croatian Cooperative Group for Hematologic Diseases (KROHEM)
Ivan Krecak, Marko Lucijanic, Rajko Kusec
Journal of Clinical Medicine.2025; 14(5): 1524. CrossRef

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Lung and Thoracic cancer

Association of TP53 Mutation Status and Sex with Clinical Outcome in Non–Small Cell Lung Cancer Treated with Immune Checkpoint Inhibitors: A Retrospective Cohort Study: Songji Choi, Se Hyun Kim, Sejoon Lee, Jeongmin Seo, Minsu Kang, Eun Hee Jung, Sang-A Kim, Koung Jin Suh, Ji Yun Lee, Ji-Won Kim, Jin Won Kim, Jeong-Ok Lee, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Jong Seok Lee; Cancer Res Treat. 2025;57(1):70-82. Published online August 7, 2024; DOI: https://doi.org/10.4143/crt.2024.046

Abstract PDF Supplementary Material PubReader ePub

Purpose
Some studies suggest that TP53 mutations are associated with the response to immune checkpoint inhibitors (ICI) in patients with non–small cell lung cancer (NSCLC) and also contribute to sex disparities in several cancers. Thus, we hypothesized that TP53 mutations might serve as sex-dependent genomic biomarkers of ICI treatment response in patients with NSCLC.
Materials and Methods
Clinical data of 100 patients with metastatic NSCLC treated with ICI monotherapy at Seoul National University Bundang Hospital (SNUBH) were retrospectively reviewed. Genomic and clinical datasets of The Cancer Genome Atlas and an ICI-treated lung cancer cohort (cBioPortal) were also analyzed.
Results
In SNUBH cohort, no statistically significant difference was observed in the median progression-free survival (PFS) according to TP53 mutation status (p=0.930); however, female patients with TP53 mutations (MT) had a significantly prolonged median PFS compared to wild-type (WT) (6.1 months in TP53 MT vs. 2.6 months in TP53 WT; p=0.021). Programmed death-ligand 1 (PD-L1) high (≥ 50%) expression was significantly enriched in female patients with TP53 MT (p=0.005). The analysis from publicly available dataset also revealed that females with NSCLC with TP53 MT showed significantly longer PFS than those with TP53 WT (p < 0.001). In The Cancer Genome Atlas analysis, expression of immune-related genes, and tumor mutation burden score in TP53 MT females were higher than in males without TP53 MT.
Conclusion
Female patients with NSCLC with TP53 mutations had high PD-L1 expression and showed favorable clinical outcomes following ICI therapy, suggesting a need for further research to explore the role of TP53 mutations for sex disparities in response to ICI therapy.

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Association Between TP53 Mutations and Platinum Resistance in a Cohort of High-Grade Serous Ovarian Cancer Patients: Novel Implications for Personalized Therapeutics
Clelia Madeddu, Eleonora Lai, Manuela Neri, Elisabetta Sanna, Giulia Gramignano, Sonia Nemolato, Mario Scartozzi, Sabrina Giglio, Antonio Macciò
International Journal of Molecular Sciences.2025; 26(5): 2232. CrossRef

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Gastrointestinal cancer

Longitudinal Comparative Analysis of Circulating Tumor DNA and Matched Tumor Tissue DNA in Patients with Metastatic Colorectal Cancer Receiving Palliative First-Line Systemic Anti-Cancer Therapy: Seung-been Lee, Ji-Won Kim, Hong-Geun Kim, Sung-Hyun Hwang, Kui-Jin Kim, Ju Hyun Lee, Jeongmin Seo, Minsu Kang, Eun Hee Jung, Koung Jin Suh, Se Hyun Kim, Jin Won Kim, Yu Jung Kim, Jee Hyun Kim, Nak-Jung Kwon, Keun-Wook Lee; Cancer Res Treat. 2024;56(4):1171-1182. Published online April 29, 2024; DOI: https://doi.org/10.4143/crt.2024.016

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study aimed to compare tumor tissue DNA (ttDNA) and circulating tumor DNA (ctDNA) to explore the clinical applicability of ctDNA and to better understand clonal evolution in patients with metastatic colorectal cancer undergoing palliative first-line systemic therapy.
Materials and Methods
We performed targeted sequencing analysis of 88 cancer-associated genes using germline DNA, ctDNA at baseline (baseline-ctDNA), and ctDNA at progressive disease (PD-ctDNA). The results were compared with ttDNA data.
Results
Among 208 consecutively enrolled patients, we selected 84 (41 males; median age, 59 years; range, 35 to 90 years) with all four sample types available. A total of 202 driver mutations were found in 34 genes. ttDNA exhibited the highest mutation frequency (n=232), followed by baseline-ctDNA (n=155) and PD-ctDNA (n=117). Sequencing ctDNA alongside ttDNA revealed additional mutations in 40 patients (47.6%). PD-ctDNA detected 13 novel mutations in 10 patients (11.9%) compared to ttDNA and baseline-ctDNA. Notably, seven mutations in five patients (6.0%) were missense or nonsense mutations in APC, TP53, SMAD4, and CDH1 genes. In baseline-ctDNA, higher maximal variant allele frequency (VAF) values (p=0.010) and higher VAF values of APC (p=0.012), TP53 (p=0.012), and KRAS (p=0.005) mutations were significantly associated with worse overall survival.
Conclusion
While ttDNA remains more sensitive than ctDNA, our ctDNA platform demonstrated validity and potential value when ttDNA was unavailable. Post-treatment analysis of PD-ctDNA unveiled new pathogenic mutations, signifying cancer’s clonal evolution. Additionally, baseline-ctDNA’s VAF values were prognostic after treatment.

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Precision-Guided Durable Response From Venetoclax With Decitabine in a Patient With a Metastatic Refractory IDH2 -Mutant Cholangiocarcinoma
Eylül Özgü, Ünal Metin Tokat, Ashkan Adibi, Şevval Nur Bilgiç, Esranur Aydın, Onur Tutar, Mutlu Demiray
JCO Precision Oncology.2025;[Epub] CrossRef

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Head and Neck cancer

Analysis of Response and Progression Patterns of Tyrosine Kinase Inhibitors in Recurrent or Metastatic Adenoid Cystic Carcinoma: A Post Hoc Analysis of Two KCSG Phase II Trials: Youjin Kim, Bhumsuk Keam, Eun Joo Kang, Jin-Soo Kim, Hye Ryun Kim, Keun-Wook Lee, Jung Hye Kwon, Kyoung Eun Lee, Yaewon Yang, Yoon Hee Choi, Min Kyoung Kim, Jun Ho Ji, Tak Yun, Moon Young Choi, Ki Hyeong Lee, Sung-Bae Kim, Myung-Ju Ahn; Cancer Res Treat. 2024;56(4):1068-1076. Published online April 15, 2024; DOI: https://doi.org/10.4143/crt.2024.008

Abstract PDF Supplementary Material PubReader ePub: Purpose
In this study, we evaluated 66 patients diagnosed with adenoid cystic carcinoma (ACC) enrolled in two Korean Cancer Study Group trials to investigate the response and progression patterns in recurrent and/or metastatic ACC treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs).
Materials and Methods
We evaluated 66 patients diagnosed with ACC who were enrolled in the Korean Cancer Study Group trials. The tumor measurements, clinical data, treatment outcomes, and progression patterns of therapy were analyzed.
Results
In the 66 patients (53 receiving axitinib and 13 receiving nintedanib), the disease control rate was 61%, and three patients achieved partial response. The median follow-up, median progression-free survival (PFS), overall survival, and 6-month PFS rate were 27.6%, 12.4%, and 18.1% months and 62.1%, respectively. Among 42 patients who experienced progression, 27 (64.3%) showed target lesion progression. Bone metastasis was an independent poor prognostic factor.
Conclusion
Overall, most patients demonstrated stable disease with prolonged PFS; however, prominent target lesion progression occurred in some patients. Thus, PFS may capture VEGFR-TKI efficacy better than the objective response rate.

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Gastrointestinal cancer

A Phase 1b/2a Study of GC1118 with 5-Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in Patients with Recurrent or Metastatic Colorectal Cancer: Keun-Wook Lee, Sae-Won Han, Tae Won Kim, Joong Bae Ahn, Ji Yeon Baek, Sang Hee Cho, Howard Lee, Jin Won Kim, Ji-Won Kim, Tae-You Kim, Yong Sang Hong, Seung-Hoon Beom, Yongjun Cha, Yoonjung Choi, Seonhui Kim, Yung-Jue Bang; Cancer Res Treat. 2024;56(2):590-601. Published online December 7, 2023; DOI: https://doi.org/10.4143/crt.2023.1117

Abstract PDF Supplementary Material PubReader ePub

Purpose
GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a).
Materials and Methods
Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m²; leucovorin 400 mg/m²; 5-fluorouracil 400 mg/m² bolus and 2,400 mg/m² infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study.
Results
RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0).
Conclusion
GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

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Drug combinations of camptothecin derivatives promote the antitumor properties
Zhen Liu, Yajie Yuan, Ning Wang, Peng Yu, Yuou Teng
European Journal of Medicinal Chemistry.2024; 279: 116872. CrossRef

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General

Impact of Patient Sex on Adverse Events and Unscheduled Utilization of Medical Services in Cancer Patients Undergoing Adjuvant Chemotherapy: A Multicenter Retrospective Cohort Study: Songji Choi, Seyoung Seo, Ju Hyun Lee, Koung Jin Suh, Ji-Won Kim, Jin Won Kim, Se Hyun Kim, Yu Jung Kim, Keun-Wook Lee, Jwa Hoon Kim, Tae Won Kim, Yong Sang Hong, Sun Young Kim, Jeong Eun Kim, Sang-We Kim, Dae Ho Lee, Jae Cheol Lee, Chang-Min Choi, Shinkyo Yoon, Su-Jin Koh, Young Joo Min, Yongchel Ahn, Hwa Jung Kim, Jin Ho Baek, Sook Ryun Park, Jee Hyun Kim; Cancer Res Treat. 2024;56(2):404-413. Published online November 7, 2023; DOI: https://doi.org/10.4143/crt.2023.784

Abstract PDF Supplementary Material PubReader ePub

Purpose
The female sex is reported to have a higher risk of adverse events (AEs) from cytotoxic chemotherapy. Few studies examined the sex differences in AEs and their impact on the use of medical services during adjuvant chemotherapy. This sub-study aimed to compare the incidence of any grade and grade ≥ 3 AEs, healthcare utilization, chemotherapy completion rate, and dose intensity according to sex.
Materials and Methods
This is a sub-study of a multicenter cohort conducted in Korea that evaluated the impact of healthcare reimbursement on AE evaluation in patients who received adjuvant chemotherapy between September 2013 and December 2016 at four hospitals in Korea.
Results
A total of 1,170 patients with colorectal, gastric, or non–small cell lung cancer were included in the study. Female patients were younger, had fewer comorbidities, and experienced less postoperative weight loss of > 10%. Females had significantly higher rates of any grade AEs including nausea, abdominal pain, stomatitis, vomiting, and neutropenia, and experienced more grade ≥ 3 neutropenia, nausea, and vomiting. The dose intensity of chemotherapy was significantly lower in females, and they also experienced more frequent dose reduction after the first cycle. Moreover, female patients receiving platinum-containing regimens had significantly higher rates of unscheduled outpatient visits.
Conclusion
Our study found that females experienced a higher incidence of multiple any-grade AEs and severe neutropenia, nausea, and vomiting, across various cancer types, leading to more frequent dose reductions. Physicians should be aware of sex differences in AEs for chemotherapy decisions.

Citations

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Cancer care for transgender and gender‐diverse people: Practical, literature‐driven recommendations from the Multinational Association of Supportive Care in Cancer
Elizabeth J. Cathcart‐Rake, Alexandre Chan, Alvaro Menendez, Denise Markstrom, Carla Schnitzlein, Yee Won Chong, Don S. Dizon
CA: A Cancer Journal for Clinicians.2025; 75(1): 68. CrossRef
Characterisation of the effects of the chemotherapeutic agent paclitaxel on neuropathic pain-related behaviour, anxiodepressive behaviour, cognition, and the endocannabinoid system in male and female rats
Chiara Di Marino, Álvaro Llorente-Berzal, Alba M. Diego, Ariadni Bella, Laura Boullon, Esther Berrocoso, Michelle Roche, David P. Finn
Frontiers in Pharmacology.2025;[Epub] CrossRef
[Translated article] Toxicity of the FOLFOX-6 regimen, with or without 5-fluorouracil bolus, in metastatic colorectal cancer
María Teresa Garrido Martínez, María Rodríguez Jorge, Ignacio García Giménez, María Isabel Guzmán Ramos, Salvador Grutzmancher Sáiz, Victoria Aviñó Tarazona
Farmacia Hospitalaria.2025;[Epub] CrossRef
The Influence of Tumor Burden Score and Lymph Node Metastasis on the Survival Benefit of Adjuvant Chemotherapy in Intrahepatic Cholangiocarcinoma
Jun Kawashima, Yutaka Endo, Selamawit Woldesenbet, Mujtaba Khalil, Miho Akabane, François Cauchy, Feng Shen, Shishir Maithel, Irinel Popescu, Minoru Kitago, Matthew J. Weiss, Guillaume Martel, Carlo Pulitano, Luca Aldrighetti, George Poultsides, Andrea Ru
Annals of Surgical Oncology.2025;[Epub] CrossRef
Toxicidad del esquema FOLFOX-6, asociado o no a bolo de 5-fluorouracilo, en cáncer colorrectal metastásico
María Teresa Garrido Martínez, María Rodríguez Jorge, Ignacio García Giménez, María Isabel Guzmán Ramos, Salvador Grutzmancher Sáiz, Victoria Aviñó Tarazona
Farmacia Hospitalaria.2024;[Epub] CrossRef

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Gastrointestinal cancer

Genomic and Transcriptomic Characterization of Gastric Cancer with Bone Metastasis: Sujin Oh, Soo Kyung Nam, Keun-Wook Lee, Hye Seung Lee, Yujun Park, Yoonjin Kwak, Kyu Sang Lee, Ji-Won Kim, Jin Won Kim, Minsu Kang, Young Suk Park, Sang-Hoon Ahn, Yun-Suhk Suh, Do Joong Park, Hyung Ho Kim; Cancer Res Treat. 2024;56(1):219-237. Published online August 11, 2023; DOI: https://doi.org/10.4143/crt.2023.340

Abstract PDF Supplementary Material PubReader ePub

Purpose
Bone metastasis (BM) adversely affects the prognosis of gastric cancer (GC). We investigated molecular features and immune microenvironment that characterize GC with BM compared to GC without BM.
Materials and Methods
Targeted DNA and whole transcriptome sequencing were performed using formalin-fixed paraffin-embedded primary tumor tissues (gastrectomy specimens) of 50 GC cases with distant metastases (14 with BM and 36 without BM). In addition, immunohistochemistry (IHC) for mucin-12 and multiplex IHC for immune cell markers were performed.
Results
Most GC cases with BM had a histologic type of poorly cohesive carcinoma and showed worse overall survival (OS) than GC without BM (p < 0.05). GC with BM tended to have higher mutation rates in TP53, KDR, APC, KDM5A, and RHOA than GC without BM. Chief cell-enriched genes (PGA3, PGC, and LIPF), MUC12, MFSD4A, TSPAN7, and TRIM50 were upregulated in GC with BM compared to GC without BM, which was correlated with poor OS (p < 0.05). However, the expression of SERPINA6, SLC30A2, PMAIP1, and ITIH2 were downregulated in GC with BM. GC with BM was associated with PIK3/AKT/mTOR pathway activation, whereas GC without BM showed the opposite effect. The densities of helper, cytotoxic, and regulatory T cells did not differ between the two groups, whereas the densities of macrophages were lower in GC with BM (p < 0.05).
Conclusion
GC with BM had different gene mutation and expression profiles than GC without BM, and had more genetic alterations associated with a poor prognosis.

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Targeted Sequencing in Gastric Cancer: Association with Tumor Molecular Characteristics and FLOT Therapy Effectiveness
Liudmila V. Spirina, Alexandra V. Avgustinovich, Olga V. Bakina, Sergey G. Afanas’ev, Maxim Yu. Volkov, Sergey V. Vtorushin, Irina V. Kovaleva, Tatyana S. Klyushina, Igor O. Munkuev
Current Issues in Molecular Biology.2024; 46(2): 1281. CrossRef
SLC30A2-Mediated Zinc Metabolism Modulates Gastric Cancer Progression via the Wnt/β-Catenin Signaling Pathway
Fan Li, Xiaohong Zhang, Li Feng, Xingxing Zhang
Frontiers in Bioscience-Landmark.2024;[Epub] CrossRef
Primary mucinous cystadenocarcinoma of the breast: A case report and literature review
Xi Cao, Yongchao Luo, Songjie Shen, Xinyu Ren
Oncology Letters.2024;[Epub] CrossRef

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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.

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Targeting fibroblast growth factor receptor (FGFR) with inhibitors in head and neck cancers: Their roles, mechanisms and challenges
Daowen Luo, Sirinart Kumfu, Nipon Chattipakorn, Siriporn C. Chattipakorn
Biochemical Pharmacology.2025; 235: 116845. CrossRef
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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3 Crossref

Gastrointestinal cancer

A Phase 3 Randomized Clinical Trial to Compare Efficacy and Safety between Combination Therapy and Monotherapy in Elderly Patients with Advanced Gastric Cancer (KCSG ST13-10): Keun-Wook Lee, Dae Young Zang, Min-Hee Ryu, Hye Sook Han, Ki Hyang Kim, Mi-Jung Kim, Sung Ae Koh, Sung Sook Lee, Dong-Hoe Koo, Yoon Ho Ko, Byeong Seok Sohn, Jin Won Kim, Jin Hyun Park, Byung-Ho Nam, In Sil Choi; Cancer Res Treat. 2023;55(4):1250-1260. Published online May 25, 2023; DOI: https://doi.org/10.4143/crt.2023.333

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study evaluated whether combination therapy is more effective than monotherapy in elderly patients with metastatic or recurrent gastric cancer (MRGC) as first-line chemotherapy.
Materials and Methods
Elderly (≥ 70 years) chemo-naïve patients with MRGC were allocated to receive either combination therapy (group A: 5-fluorouracil [5-FU]/oxaliplatin, capecitabine/oxaliplatin, capecitabine/cisplatin, or S-1/cisplatin) or monotherapy (group B: 5-FU, capecitabine, or S-1). In group A, starting doses were 80% of standard doses, and they could be escalated to 100% at the discretion of the investigator. Primary endpoint was to confirm superior overall survival (OS) of combination therapy vs. monotherapy.
Results
After 111 of the planned 238 patients were randomized, enrollment was terminated due to poor accrual. In the full-analysis population (group A [n=53] and group B [n=51]), median OS of combination therapy vs. monotherapy was 11.5 vs. 7.5 months (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.56 to 1.30; p=0.231). Median progression-free survival (PFS) was 5.6 vs. 3.7 months (HR, 0.53; 95% CI, 0.34 to 0.83; p=0.005). In subgroup analyses, patients aged 70-74 years tended to have superior OS with combination therapy (15.9 vs. 7.2 months, p=0.056). Treatment-related adverse events (TRAEs) occurred more frequently in group A vs. group B. However, among severe TRAEs (≥ grade 3), there were no TRAEs with a frequency difference of > 5%.
Conclusion
Combination therapy was associated with numerically improved OS, although statistically insignificant, and a significant PFS benefit compared with monotherapy. Although combination therapy showed more frequent TRAEs, there was no difference in the frequency of severe TRAEs.

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A prognostic nomogram to predict the cancer-specific survival of patients with initially diagnosed metastatic gastric cancer: a validation study in a Chinese cohort
Ziming Zhao, Erxun Dai, Bao Jin, Ping Deng, Zulihaer Salehebieke, Bin Han, Rongfan Wu, Zhaowu Yu, Jun Ren
Clinical and Translational Oncology.2024; 27(1): 135. CrossRef

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Palliative medicine

A Prognostic Model to Facilitate Palliative Care Referral in Oncology Outpatients: Yu Jung Kim, Yusuke Hiratsuka, Sang-Yeon Suh, Beodeul Kang, Si Won Lee, Hong-Yup Ahn, Koung Jin Suh, Ji-Won Kim, Se Hyun Kim, Jin Won Kim, Keun-Wook Lee, Jee Hyun Kim, Jong Seok Lee; Cancer Res Treat. 2022;54(2):621-629. Published online July 12, 2021; DOI: https://doi.org/10.4143/crt.2021.483

Abstract PDF PubReader ePub

Purpose
We aimed to develop a prognostic model to assist palliative care referral at least 3 months before death in advanced cancer patients treated at an outpatient medical oncology clinic.
Materials and Methods
In this prospective cohort study, a total of 200 patients were enrolled at a tertiary cancer center in South Korea. The major eligibility criterion was an expected survival of less than a year as estimated by their oncologists. We analyzed the influences of known prognostic factors along with chemotherapy status, mid-arm circumference, and triceps skinfold thickness on survival time.
Results
The mean age of the patients was 64.5 years, 36% were female, and the median survival time was 7.6 months. In the multivariate analysis, we found 6 significant factors related to poor survival: a poor Eastern Cooperative Oncology Group (ECOG) performance status (≥2), not undergoing chemotherapy, anorexia, a low lymphocyte level (<12%), a high lactate dehydrogenase (LDH) level (≥300 IU/L), and a low mid-arm circumference (<23 cm). We developed a prognostic model (score, 0-8.0) to predict 3-month survival based on the multivariate analysis. Patients who scored ≥4.0 points had a short survival of less than 3 months (p<0.001). The discriminating ability of the prognostic model using the area under the receiver operating characteristic curve (AUC) was 0.88.
Conclusion
The prognostic model using ECOG performance status, chemotherapy status, anorexia, lymphocytes, LDH, and mid-arm circumference can predict 3-month survival in medical oncology outpatients. It can alert oncologists to refer patients to palliative care specialists before it is too late.

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Clinicians’ Prediction of Survival Is Most Useful for Palliative Care Referral
Eun Hee Jung, Yusuke Hiratsuka, Sang-Yeon Suh, Seok-Joon Yoon, Beodeul Kang, Si Won Lee, Koung Jin Suh, Ji-Won Kim, Se Hyun Kim, Jin Won Kim, Keun-Wook Lee, Yu Jung Kim
Palliative Medicine Reports.2024; 5(1): 365. CrossRef

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Head and Neck cancer

Induction Chemotherapy as a Prognostication Index and Guidance for Treatment of Locally Advanced Head and Neck Squamous Cell Carcinoma: The Concept of Chemo-Selection (KCSG HN13-01): Yun-Gyoo Lee, Eun Joo Kang, Bhumsuk Keam, Jin-Hyuk Choi, Jin-Soo Kim, Keon Uk Park, Kyoung Eun Lee, Hyo Jung Kim, Keun-Wook Lee, Min Kyoung Kim, Hee Kyung Ahn, Seong Hoon Shin, Hye Ryun Kim, Sung-Bae Kim, Hwan Jung Yun; Cancer Res Treat. 2022;54(1):109-117. Published online April 27, 2021; DOI: https://doi.org/10.4143/crt.2020.1329

Abstract PDF PubReader ePub

Purpose
Certain patient subgroups who do not respond to induction chemotherapy (IC) show inherent chemoresistance in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). This study aimed to assess the prognostic value of IC, and role of IC in guiding the selection of a definitive locoregional therapy.
Materials and Methods
Out of the 445 patients in multi-institutional LA-HNSCC cohort, 158 (36%) receiving IC were enrolled. The study outcome was to assess overall survival (OS) through IC responsiveness and its role to select subsequent treatments.
Results
Among 135 patients who completed subsequent treatment following IC, 74% responded to IC (complete response in 17% and partial response in 58%). IC-non-responders showed 4.5 times higher risk of mortality than IC-responders (hazard ratio, 4.52; 95% confidence interval, 2.32 to 8.81; p < 0.001). Among IC-responders, 84% subsequently received definitive concurrent chemoradiotherapy (CCRT) and OS was not differed by surgery or CCRT (p=0.960). Regarding IC-non-responders, 54% received CCRT and 46% underwent surgery, and OS was poor in CCRT (24-month survival rate of 38%) or surgery (24-month survival rate of 63%).
Conclusion
Response to IC is a favorable prognostic factor. For IC-responders, either surgery or CCRT achieved similar survival probabilities. For IC-non-responder, multidisciplinary approach was warranted reflecting patients’ preference, morbidity, and prognosis.

Citations

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Circulating tumor DNA determines induction chemotherapy response in HPV associated oropharyngeal squamous cell carcinoma: A pilot study
Zachary M. Huttinger, Emile Gogineni, Sujith Baliga, Dukagjin M. Blakaj, Priyanka Bhateja, Marcelo Bonomi, Stephen Y. Kang, Matthew O. Old, Nolan B. Seim, Kyle K. VanKoevering, Amit Agrawal, Enver Ozer, James W. Rocco, Catherine T. Haring
Oral Oncology.2025; 161: 107179. CrossRef
Clinical decision pathway and management of locally advanced head and neck squamous cell carcinoma: A multidisciplinary consensus in Asia-Pacific
Ye Guo, Torahiko Nakashima, Byoung Chul Cho, Darren W.-T. Lim, Muh-Hwa Yang, Pei-Jen Lou, June Corry, Jin Ching Lin, Guo Pei Zhu, Kyung Hwan Kim, Bin Zhang, Zhiming Li, Ruey-Long Hong, Junice Yi Siu Ng, Ee Min Tan, Yan Ping Liu, Con Stylianou, Carmel Spit
Oral Oncology.2024; 148: 106657. CrossRef
Neoadjuvant programmed cell death 1 blockade combined with chemotherapy for locally advanced head and neck squamous cell carcinoma
Ping Han, Faya Liang, Pan Song, Taowei Wu, Yangyang Li, Ming Gao, Peiliang Lin, Jianming Fan, Xiaoming Huang
Holistic Integrative Oncology.2024;[Epub] CrossRef
Clinical prognostic factors to guide treatment strategy for HPV‑positive oropharyngeal cancer using treatment outcomes of induction chemotherapy: A real‑world experience
Hyun Bang, Hyeon-Jong Kim, Seung Lee, Hyun Shim, Jun Hwang, Woo Bae, Ik-Joo Chung, Sang-Hee Cho
Oncology Letters.2024;[Epub] CrossRef
Role of induction chemotherapy in advanced‐stage olfactory neuroblastoma
Sung‐Woo Cho, Bhumsuk Keam, Keun‐Wook Lee, Ji‐Won Kim, Doo Hee Han, Hyun Jik Kim, Jeong‐Whun Kim, Dong‐Young Kim, Chae‐Seo Rhee, Yun Jung Bae, Ji‐Hoon Kim, Keun‐Yong Eom, Hong‐Gyun Wu, Yong Hwy Kim, Chae‐Yong Kim, Sun Ha Paek, Hyojin Kim, Tae‐Bin Won
International Forum of Allergy & Rhinology.2024; 14(12): 1882. CrossRef
Intra-Arterial Chemotherapy for Locally Advanced Oral Cavity Cancer
B. B. Vyzhigina, M. A. Kropotov, B. I. Dolgushin, D. A. Safarov, I. V. Pogrebnyakov, S. B. Alieva
Journal of oncology: diagnostic radiology and radiotherapy.2024; 7(3): 62. CrossRef
Response to induction chemotherapy as a prognostic indicator in locally advanced head and neck squamous cell carcinoma
Francesca Huwyler, Roland Giger, Ruben Bill, Daniel Rauch, Simon Haefliger
Journal of Cancer Research and Clinical Oncology.2024;[Epub] CrossRef
Response to induction chemotherapy in sinonasal malignancies: A single‐institutional experience
Sarah C. Nyirjesy, Rachel Fenberg, Margaret A. Heller, Ryan T. Judd, Michael M. Li, Brandon Koch, Marcelo Bonomi, Ricardo L. Carrau, Kyle K. VanKoevering
Head & Neck.2023; 45(6): 1445. CrossRef
Human Papillomavirus-Related Non-Metastatic Oropharyngeal Carcinoma: Current Local Treatment Options and Future Perspectives
Michaela Svajdova, Pavol Dubinsky, Tomas Kazda, Branislav Jeremic
Cancers.2022; 14(21): 5385. CrossRef

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Head and Neck Cancer

Outcomes and Biomarkers of Immune Checkpoint Inhibitor Therapy in Patients with Refractory Head and Neck Squamous Cell Carcinoma: KCSG HN18-12: Yun-Gyoo Lee, Hyun Chang, Bhumsuk Keam, Sang Hoon Chun, Jihyun Park, Keon Uk Park, Seong Hoon Shin, Ho Jung An, Kyoung Eun Lee, Keun-Wook Lee, Hye Ryun Kim, Sung-Bae Kim, Myung-Ju Ahn, In Gyu Hwang; Cancer Res Treat. 2021;53(3):671-677. Published online December 7, 2020; DOI: https://doi.org/10.4143/crt.2020.824

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study was conducted to determine the effectiveness of immune checkpoint inhibitors (ICIs) in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) after platinum-containing chemotherapy. We also identified clinical biomarkers which may be predictive of patient prognosis.
Materials and Methods
We analyzed 125 patients with R/M HNSCC who received ICIs, retrospectively. Overall response rate (ORR) was the primary study outcome. Overall survival (OS) and progression-free survival (PFS) were the secondary study outcomes.
Results
The patients received anti–programmed cell death protein-1 (PD-1) (n=73, 58%), anti–programmed death-ligand 1 (PD-L1) (n=24, 19%), or a combination of anti–PD-1/PD-L1 and anti–cytotoxic T-lymphocyte antigen 4 (n=28, 22%). The median age was 57 years (range, 37 to 87). The location of the primary tumor was in the oral cavity in 28% of the cases, followed by oropharynx (27%), hypopharynx (20%), and larynx (12%). The ORR was 15% (19/125). With 12.3 months of median follow-up, median PFS was 2.7 months. Median OS was 10.8 months. A neutrophil-to-lymphocyte ratio (NLR) > 4 was significantly associated with poor response to ICIs (odds ratio, 0.30; p=0.022). A sum of the target lesions > 40 mm (hazard ratio [HR], 1.53; p=0.046] and a NLR > 4 (HR, 1.75; p=0.009) were considered to be predictive markers of short PFS. A poor performance status (HR, 4.79; p < 0.001), a sum of target lesions > 40 mm (HR, 1.93; p=0.025), and an NLR > 4 (HR, 3.36; p < 0.001) were the significant predictors for poor survival.
Conclusion
ICIs exhibited favorable antitumor activity in R/M HNSCC. Clinically, our findings can be used to recognize patients benefit from receiving ICI.

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Angeline A. Truong, Rex H. Lee, Xin Wu, Alain P. Algazi, Hyunseok Kang, Ivan H. El‐Sayed, Jonathan R. George, Chase M. Heaton, William R. Ryan, Yena Jeon, Mi‐Ok Kim, Patrick K. Ha, Katherine C. Wai
Otolaryngology–Head and Neck Surgery.2025; 172(2): 548. CrossRef
Risk Factors for Progressive Disease After Immune Checkpoint Inhibitor Therapy in Head and Neck Squamous Cell Carcinoma
Seo Yoon Jang, Yun‐Gyoo Lee, Sang Hoon Chun, Ji Hyun Park, Keon Uk Park, Hyun Chang, Keun‐Wook Lee, Hye Ryun Kim, Seong Hoon Shin, Ho Jung An, Kyoung Eun Lee, In Gyu Hwang, Myung‐Ju Ahn, Sung‐Bae Kim, Bhumsuk Keam
Head & Neck.2025;[Epub] CrossRef
Pretreatment neutrophil-to-lymphocyte ratio is associated with immunotherapy efficacy in patients with advanced cancer: a systematic review and meta-analysis
Jialin Su, Yuning Li, Shuhua Tan, Tianli Cheng, Yongzhong Luo, Lemeng Zhang
Scientific Reports.2025;[Epub] CrossRef
Neutrophil‐to‐Lymphocyte Ratio as a Predictor for PD‐L1 Inhibitor Treatment in Recurrent or Metastatic Nasopharyngeal Carcinoma
Kun Gao, Zhigong Wei, Zheran Liu, Yiyan Pei, Huilin Li, Ge Song, Jin Xiang, Junyou Ge, Yan Qing, Youneng Wei, Ping Ai, Ye Chen, Xingchen Peng
Head & Neck.2025;[Epub] CrossRef
Impact of PIK3CA and cell cycle pathway genetic alterations on durvalumab efficacy in patients with head and neck squamous cell carcinoma: Post hoc analysis of TRIUMPH study
Dong Hyun Kim, Seung Taek Lim, Hye Ryun Kim, Eun Joo Kang, Hee Kyung Ahn, Yun-Gyoo Lee, Der Sheng Sun, Jung Hye Kwon, Sang-Cheol Lee, Hyun Woo Lee, Min Kyoung Kim, Bhumsuk Keam, Keon-Uk Park, Seong-Hoon Shin, Hwan Jung Yun
Oral Oncology.2024; 151: 106739. CrossRef
Characterization of macrophages in head and neck squamous cell carcinoma and development of MRG-based risk signature
Lei Liu, Qiang Liu
Scientific Reports.2024;[Epub] CrossRef
Inflammatory markers as prognostic markers in patients with head and neck squamous cell carcinoma treated with immune checkpoint inhibitors: a systematic review and meta-analysis
Quan Wang, Xiangzhi Yin, Shengxia Wang, Haijun Lu
Frontiers in Oncology.2024;[Epub] CrossRef
Predictive value of early dynamic changes of NLR and PLR for the efficacy of immune checkpoint inhibitor in head and neck squamous cell carcinoma
Dong Hyun Kim, Seo Yoon Jang, Bhumsuk Keam
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology.2024; 138(6): 763. CrossRef
Diagnostic Predictors of Immunotherapy Response in Head and Neck Squamous Cell Carcinoma
Piero Giuseppe Meliante, Federica Zoccali, Marco de Vincentiis, Massimo Ralli, Carla Petrella, Marco Fiore, Antonio Minni, Christian Barbato
Diagnostics.2023; 13(5): 862. CrossRef
Patterns of recurrence in head and neck squamous cell carcinoma to inform personalized surveillance protocols
Catherine T. Haring, Lulia A. Kana, Sarah M. Dermody, Collin Brummel, Jonathan B. McHugh, Keith A. Casper, Steven B. Chinn, Kelly M. Malloy, Michelle Mierzwa, Mark E. P. Prince, Andrew J. Rosko, Jennifer Shah, Chaz L. Stucken, Andrew G. Shuman, J. Chad Br
Cancer.2023; 129(18): 2817. CrossRef
Immunotherapy with PD-1 Inhibitor Nivolumab in Recurrent/Metastatic Platinum Refractory Head and Neck Cancers—Early Experiences from Romania and Literature Review
Camil Ciprian Mireștean, Mihai Cosmin Stan, Michael Schenker, Constantin Volovăț, Simona Ruxandra Volovăț, Dragoș Teodor Petru Iancu, Roxana Irina Iancu, Florinel Bădulescu
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Integrating Cutting-Edge Methods to Oral Cancer Screening, Analysis, and Prognosis
Sagar Dholariya, Ragini D. Singh, Amit Sonagra, Dharamveer Yadav, Bhairavi N. Vajaria, Deepak Parchwani
Critical Reviews™ in Oncogenesis.2023; 28(2): 11. CrossRef
Neutrophil–lymphocyte ratio and platelet–lymphocyte ratio as potential predictive markers of treatment response in cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis
Tibera K. Rugambwa, Omar Abdihamid, Xiangyang Zhang, Yinghui Peng, Changjing Cai, Hong Shen, Shan Zeng, Wei Qiu
Frontiers in Oncology.2023;[Epub] CrossRef
Characterization of Age-Associated, Neutrophil-to-Lymphocyte Ratio (NLR) and Systemic Immune-Inflammatory Index (SII) as Biomarkers of Inflammation in Geriatric Patients with Cancer Treated with Immune Checkpoint Inhibitors: Impact on Efficacy and Surviva
Khalil Choucair, Caroline Nebhan, Alessio Cortellini, Stijn Hentzen, Yinghong Wang, Cynthia Liu, Raffaele Giusti, Marco Filetti, Paolo Antonio Ascierto, Vito Vanella, Domenico Galetta, Annamaria Catino, Nour Al-Bzour, Azhar Saeed, Ludimila Cavalcante, Pam
Cancers.2023; 15(20): 5052. CrossRef
A systematic review and meta-analysis of prognostic indicators in patients with head and neck malignancy treated with immune checkpoint inhibitors
Dengxiong Kang, Siping Liu, Xin Yuan, Shenxiang Liu, Zhengrong Zhang, Zhilian He, Xudong Yin, Haiyan Mao
Journal of Cancer Research and Clinical Oncology.2023; 149(20): 18215. CrossRef
Prognostic value of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio during immune checkpoint inhibitor treatment in recurrent or metastatic head and neck squamous cell carcinoma patients
Jun-Liang Li, Tsai-Ling Hsieh, Ming-Che Ou, Frank Cheau-Feng Lin, Stella Chin-Shaw Tsai
Oral Oncology.2022; 126: 105729. CrossRef
Neutrophil‐to‐lymphocyte ratio as a prognostic marker for head and neck squamous cell carcinoma treated with immune checkpoint inhibitors: Meta‐analysis
Yukinori Takenaka, Ryohei Oya, Norihiko Takemoto, Hidenori Inohara
Head & Neck.2022; 44(5): 1237. CrossRef
Safety and Efficacy of Influenza Vaccination in Patients Receiving Immune Checkpoint Inhibitors. Systematic Review with Meta-Analysis
Maria A. Lopez-Olivo, Valeria Valerio, Aliza R. Karpes Matusevich, Marianela Brizio, Michelle Kwok, Yimin Geng, Maria E. Suarez-Almazor, Ines Colmegna
Vaccines.2022; 10(8): 1195. CrossRef
Identification of Immune-Related LncRNA Pairs for Predicting Prognosis and Immunotherapeutic Response in Head and Neck Squamous Cell Carcinoma
Xueying Wang, Kui Cao, Erliang Guo, Xionghui Mao, Lunhua Guo, Cong Zhang, Junnan Guo, Gang Wang, Xianguang Yang, Ji Sun, Susheng Miao
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Roles of Major RNA Adenosine Modifications in Head and Neck Squamous Cell Carcinoma
Xing-xing Huo, Shu-jie Wang, Hang Song, Ming-de Li, Hua Yu, Meng Wang, Hong-xiao Gong, Xiao-ting Qiu, Yong-fu Zhu, Jian-ye Zhang
Frontiers in Pharmacology.2021;[Epub] CrossRef

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Gastrointestinal cancer

Adjuvant Chemotherapy in Microsatellite Instability–High Gastric Cancer: Jin Won Kim, Sung-Yup Cho, Jeesoo Chae, Ji-Won Kim, Tae-Yong Kim, Keun-Wook Lee, Do-Youn Oh, Yung-Jue Bang, Seock-Ah Im; Cancer Res Treat. 2020;52(4):1178-1187. Published online June 11, 2020; DOI: https://doi.org/10.4143/crt.2020.313

Abstract PDF Supplementary Material PubReader ePub

Purpose
Microsatellite instability (MSI) status may affect the efficacy of adjuvant chemotherapy in gastric cancer. In this study, the clinical characteristics of MSI-high (MSI-H) gastric cancer and the predictive value of MSI-H for adjuvant chemotherapy in large cohorts of gastric cancer patients were evaluated. Material and Methods This study consisted of two cohorts. Cohort 1 included gastric cancer patients who received curative resection with pathologic stage IB-IIIC. Cohort 2 included patients with MSI-H gastric cancer who received curative resection with pathologic stage II/III. MSI was examined using two mononucleotide markers and three dinucleotide markers.
Results
Of 359 patients (cohort 1), 41 patients (11.4%) had MSI-H. MSI-H tumors were more frequently identified in older patients (p < 0.001), other histology than poorly cohesive, signet ring cell type (p=0.005), intestinal type (p=0.028), lower third tumor location (p=0.005), and absent perineural invasion (p=0.027). MSI-H status has a tendency of better disease-free survival (DFS) and overall survival (OS) in multivariable analyses (hazard ratio [HR], 0.4; p=0.059 and HR, 0.4; p=0.063, respectively). In the analysis of 162 MSI-H patients (cohort 2), adjuvant chemotherapy showed a significant benefit with respect to longer DFS and OS (p=0.047 and p=0.043, respectively). In multivariable analysis, adjuvant chemotherapy improved DFS (HR, 0.4; p=0.040).
Conclusion
MSI-H gastric cancer had distinct clinicopathologic findings. Even in MSI-H gastric cancer of retrospective cohort, adjuvant chemotherapy could show a survival benefit, which was in contrast to previous prospective studies and should be investigated in a further prospective trial.

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Management of Microsatellite Instability High (MSI-H) Gastroesophageal Adenocarcinoma
Katherine I. Zhou, Brent A. Hanks, John H. Strickler
Journal of Gastrointestinal Cancer.2024; 55(2): 483. CrossRef
The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023
Feng‐Hua Wang, Xiao‐Tian Zhang, Lei Tang, Qi Wu, Mu‐Yan Cai, Yuan‐Fang Li, Xiu‐Juan Qu, Hong Qiu, Yu‐Jing Zhang, Jie‐Er Ying, Jun Zhang, Ling‐Yu Sun, Rong‐Bo Lin, Chang Wang, Hao Liu, Miao‐Zhen Qiu, Wen‐Long Guan, Sheng‐Xiang Rao, Jia‐Fu Ji, Yan Xin, Wei‐
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Clinical Significance of Fibrinogen and Platelet to Pre-Albumin Ratio in Predicting the Prognosis of Advanced Gastric Cancer
Huakai Tian, Zitao Liu, Zuo Zhang, Lipeng Zhang, Zhen Zong, Jiang Liu, Houqun Ying, Hui Li
Journal of Inflammation Research.2023; Volume 16: 4373. CrossRef
Fatty acid metabolism is related to the immune microenvironment changes of gastric cancer and RGS2 is a new tumor biomarker
Shifeng Yang, Boshi Sun, Wenjing Li, Hao Yang, Nana Li, Xinyu Zhang
Frontiers in Immunology.2022;[Epub] CrossRef
Chemotherapy in Neuroendocrine Tumors
Satya Das, Taymeyah Al-Toubah, Jonathan Strosberg
Cancers.2021; 13(19): 4872. CrossRef

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5 Crossref

A Phase II Study of Avelumab Monotherapy in Patients with Mismatch Repair–Deficient/Microsatellite Instability–High or POLE-Mutated Metastatic or Unresectable Colorectal Cancer: Jwa Hoon Kim, Sun Young Kim, Ji Yeon Baek, Yong Jun Cha, Joong Bae Ahn, Han Sang Kim, Keun-Wook Lee, Ji-Won Kim, Tae-You Kim, Won Jin Chang, Joon Oh Park, Jihun Kim, Jeong Eun Kim, Yong Sang Hong, Yeul Hong Kim, Tae Won Kim; Cancer Res Treat. 2020;52(4):1135-1144. Published online April 24, 2020; DOI: https://doi.org/10.4143/crt.2020.218

Abstract PDF Supplementary Material PubReader ePub

Purpose
We evaluated the efficacy and safety of avelumab, an anti-PD-L1 antibody, in patients with metastatic or unresectable colorectal cancer (mCRC) with mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) or POLE mutations.
Materials and Methods
In this prospective, open-label, multicenter phase II study, 33 patients with mCRC harboring dMMR/MSI-H or POLE mutations after failure of ≥1st-line chemotherapy received avelumab 10 mg/kg every 2 weeks. dMMR/MSI-H was confirmed with immunohistochemical staining (IHC) by loss of expression of MMR proteins or polymerase chain reaction (PCR) for microsatellite sequences. POLE mutation was confirmed by next-generation sequencing (NGS). The primary endpoint was the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors ver. 1.1.
Results
The median age was 60 years, and 78.8% were male. Thirty patients were dMMR/MSI-H and three had POLE mutations. The ORR was 24.2%, and all of the responders were dMMR/MSI-H. For 21 patients with MSI-H by PCR or NGS, the ORR was 28.6%. At a median follow-up duration of 16.3 months, median progression-free survival and overall survival were 3.9 and 13.2 months in all patients, and 8.1 months and not reached, respectively, in patients with MSI-H by PCR or NGS. Dose interruption and discontinuation due to treatment-related adverse events occurred in 4 and 2 patients, respectively, with no treatment-related deaths.
Conclusion
Avelumab displayed antitumor activity with manageable toxicity in patients with previously treated mCRC harboring dMMR/MSI-H. Diagnosis of dMMR/MSI-H with PCR or NGS could be complementary to IHC to select patients who would benefit from immunotherapy.

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Mariam Rojas, Clara Rodrigo, Reinaldo Moreno, Marta Cascante, Joan Maurel
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Ye Yang, Su Fang Wu, Wei Bao
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Jonadab E Olguin, Monica G Mendoza-Rodriguez, C Angel Sanchez-Barrera, Luis I Terrazas
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Ruiqi Wang, Dan Cong, Yuansong Bai, Wenlong Zhang
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PD-L1 Testing in Gastric Cancer by the Combined Positive Score of the 22C3 PharmDx and SP263 Assay with Clinically Relevant Cut-offs: Yujun Park, Jiwon Koh, Hee Young Na, Yoonjin Kwak, Keun-Wook Lee, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Hye Seung Lee; Cancer Res Treat. 2020;52(3):661-670. Published online January 10, 2020; DOI: https://doi.org/10.4143/crt.2019.718

Abstract PDF Supplementary Material PubReader ePub

Purpose
We provide a comparison between 22C3 pharmDx and SP263 assay, for evaluating programmed death ligand 1 (PD-L1) expression in advanced gastric cancer (GC) patients.
Materials and Methods
The PD-L1 immunohistochemistry by 22C3 pharmDx and SP263 assays was performed in the center of the tumor (CT) and invasive margin (IM) in 379 GC tissues using tissue microarrays and interpreted as combined positive score (CPS) and tumor proportion score (TPS). Of the total samples, 55 samples were independently reviewed by five pathologists.
Results
The two assays showed a high correlation in both the CPS and TPS. At a CPS ≥ 1 cut-off, 219 (57.8%) and 231 (60.9%) GCs were positive for PD-L1 with the 22C3 and SP263 assays, and at ≥ 10 cut-off, 37 (9.8%) and 36 (9.5%) GCs were positive, respectively. The overall percent agreement (OPA) was greater than 90% with CPS ≥ 1 and ≥ 10 cut-offs, and TPS ≥ 1% and ≥ 10% cut-offs. There was higher OPA between the two assays with a CPS cut-off ≥ 10 (99.2%) than ≥ 1 (94.7%). The percent agreement between the CT and IM was higher with a CPS cut-off ≥ 10 (92.9%) than ≥ 1 (77.6%). Patient with positive expression at CPS ≥ 5 cut-off had a significantly better outcomes in both assays. Interobserver variability among five pathologists was higher than the assay variability.
Conclusion
Two assays for PD-L1 expression in GC showed high agreement. These results provide guidance for selecting eligible patients with GC for pembrolizumab treatment.

Citations

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Effect of Platinum-Based Chemotherapy on PD-L1 Expression on Tumor Cells in Non-small Cell Lung Cancer: Junghoon Shin, Jin-Haeng Chung, Se Hyun Kim, Kyu Sang Lee, Koung Jin Suh, Ji Yun Lee, Ji-Won Kim, Jeong-Ok Lee, Jin-Won Kim, Yu-Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Jong-Seok Lee; Cancer Res Treat. 2019;51(3):1086-1097. Published online November 5, 2018; DOI: https://doi.org/10.4143/crt.2018.537

Abstract PDF PubReader ePub

Purpose
Programmed death-1 (PD-1)/PD-1 ligand (PD-L1) axis blockades have revolutionized the treatment of advanced non-small cell lung cancer (NSCLC). We assessed the effect of platinum-based chemotherapy on tumor PD-L1 expression and its clinical implications.
Materials and Methods
We used immunohistochemistry to retrospectively evaluate the percentage of tumor cells with membranous PD-L1 staining (tumor proportion score) in paired tumor specimens obtained before and after platinum-based neoadjuvant chemotherapy (NACT) in 86 patients with NSCLC. We analyzed the correlation between the change in PD-L1 tumor proportion score and clinicopathologic characteristics, response to NACT, and survival.
Results
The PD-L1 tumor proportion score increased in a significant proportion of patients with NSCLC after platinum-based NACT (Wilcoxon signed-rank test, p=0.002). That pattern was consistent across clinically defined subgroups except for patients with partial response to NACT. Tumors from 26 patients (30.2%) were PD-L1‒negative before NACT but PD-L1-positive after NACT, whereas the reverse pattern occurred in six patients (7%) (McNemar’s test, p < 0.001). Increase in PD-L1 tumor proportion score was significantly associated with lack of response to NACT (Fisher exact test, p=0.015). There was a tendency, albeit not statistically significant, for patients with an increase in PD-L1 tumor proportion score to have shorter survival.
Conclusion
Tumor PD-L1 expression increased after platinum-based NACT in a significant proportion of patients with NSCLC. Increase in tumor PD-L1 expression may predict poor clinical outcome.

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11,426 View
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61 Web of Science
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Treatment Patterns and Changes in Quality of Life during First-Line Palliative Chemotherapy in Korean Patients with Advanced Gastric Cancer: Jin Won Kim, Jong Gwang Kim, Byung Woog Kang, Ik-Joo Chung, Young Seon Hong, Tae-You Kim, Hong Suk Song, Kyung Hee Lee, Dae Young Zang, Yoon Ho Ko, Eun-Kee Song, Jin Ho Baek, Dong‐Hoe Koo, So Yeon Oh, Hana Cho, Keun-Wook Lee; Cancer Res Treat. 2019;51(1):223-239. Published online October 19, 2018; DOI: https://doi.org/10.4143/crt.2018.073

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to evaluate chemotherapy patterns and changes in quality of life (QOL) during first-line palliative chemotherapy for Korean patients with unresectable or metastatic/recurrent gastric cancer (GC).
Materials and Methods
Thiswas a non-interventional, multi-center, prospective, observational study of 527 patients in Korea. QOL assessments were conducted using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30 and QLQ-STO22 every 3 months over a 12-month period during first-line palliative chemotherapy. The specific chemotherapy regimens were selected by individual clinicians.
Results
Most patients (93.2%) received combination chemotherapy (mainly fluoropyrimidine plus platinum) as their first-line palliative chemotherapy. The median progression-free survival and overall survival were 8.2 and 14.8 months, respectively. Overall, “a little” changes (differences of 5-10 points from baseline)were observed in some of the functioning or symptom scales; none of the QOL scales showed either “moderate” or “very much” change (i.e., ≥ 11 point difference from baseline). When examining the best change in each QOL domain from baseline, scales related to some aspects of functioning, global health status/QOL, and most symptoms revealed significant improvements (p < 0.05). Throughout the course of first-line palliative chemotherapy, most patients’ QOL was maintained to a similar degree, regardless of their actual response to chemotherapy.
Conclusion
This observational study provides important information on the chemotherapy patterns and QOL changes in Korean patientswith advanced GC. Overall, first-line palliative chemotherapy was found to maintain QOL, and most parameters showed an improvement compared with the baseline at some point during the course.

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Health-related quality of life with bemarituzumab plus mFOLFOX6 in patients with FGFR2b-overexpressing, advanced gastric or gastroesophageal junction cancer
Z.A. Wainberg, P.C. Enzinger, S. Qin, K. Yamaguchi, J. Wang, X. Zhou, A. Gnanasakthy, K. Taylor, A. Yusuf, I. Majer, A. Jamotte, Y.-K. Kang
ESMO Gastrointestinal Oncology.2024; 6: 100095. CrossRef
Impact of systemic cancer treatment on quality of life and mental well-being: a comparative analysis of patients with localized and advanced cancer
Adán Rodríguez-Gonzalez, Alberto Carmona-Bayonas, Raquel Hernandez San Gil, Patricia Cruz-Castellanos, Mónica Antoñanzas-Basa, David Lorente-Estelles, María Jose Corral, Manuel González-Moya, Oscar Alfredo Castillo-Trujillo, Emilio Esteban, Paula Jiménez-
Clinical and Translational Oncology.2023; 25(12): 3492. CrossRef
Reminiscence therapy-based care program alleviates anxiety and depression, as well as improves the quality of life in recurrent gastric cancer patients
Xing Wu, Weiwei Zhang
Frontiers in Psychology.2023;[Epub] CrossRef
Toxicities and Quality of Life during Cancer Treatment in Advanced Solid Tumors
Eun Mi Lee, Paula Jiménez-Fonseca, Rocio Galán-Moral, Sara Coca-Membribes, Ana Fernández-Montes, Elena Sorribes, Esmeralda García-Torralba, Laura Puntí-Brun, Mireia Gil-Raga, Juana Cano-Cano, Caterina Calderon
Current Oncology.2023; 30(10): 9205. CrossRef
Psychosocial functioning in individuals with advanced oesophago-gastric cancer: a mixed methods systematic review
Cara Ghiglieri, Martin Dempster, Sam Wright, Lisa Graham-Wisener
BMC Palliative Care.2023;[Epub] CrossRef
Multicenter phase III trial of S-1 and cisplatin versus S-1 and oxaliplatin combination chemotherapy for first-line treatment of advanced gastric cancer (SOPP trial)
Keun-Wook Lee, Ik-Joo Chung, Min-Hee Ryu, Young Iee Park, Byung-Ho Nam, Ho-Suk Oh, Kyung Hee Lee, Hye Sook Han, Bong-Gun Seo, Jae-Cheol Jo, Hyo Rak Lee, Jin Won Kim, Sook Ryun Park, Sang Hee Cho, Yoon-Koo Kang
Gastric Cancer.2021; 24(1): 156. CrossRef
Effect of early tumor response on the health-related quality of life among patients on second-line chemotherapy for advanced gastric cancer in the ABSOLUTE trial
Kazumasa Fujitani, Kohei Shitara, Atsuo Takashima, Keisuke Koeda, Hiroki Hara, Norisuke Nakayama, Shuichi Hironaka, Kazuhiro Nishikawa, Yutaka Kimura, Kenji Amagai, Hisashi Hosaka, Yoshito Komatsu, Ken Shimada, Ryohei Kawabata, Hideki Ohdan, Yasuhiro Kode
Gastric Cancer.2021; 24(2): 467. CrossRef
Quality-of-Life Assessment in Patients Receiving Palliative Chemotherapy: Call for Action
Maheswari Senthil
Annals of Surgical Oncology.2021; 28(1): 7. CrossRef
Impact of gastric cancer treatment on quality of life of patients
Kerstin Schütte, Christian Schulz, Kristina Middelberg-Bisping
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Influencing Factors and Effects of Treatment on Quality of Life in Patients With Gastric Cancer—A Systematic Review
Sophia Kristina Rupp, Andreas Stengel
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Chronological changes in quality of life and body composition after gastrectomy for locally advanced gastric cancer
Ki Bum Park, Ji Yeon Park, Seung Soo Lee, Ho Young Chung, Oh Kyoung Kwon
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Viennese risk prediction score for Advanced Gastroesophageal carcinoma based on Alarm Symptoms (VAGAS score): characterisation of alarm symptoms in advanced gastro-oesophageal cancer and its correlation with outcome
Hannah Christina Puhr, Eleonore Pablik, Anna Sophie Berghoff, Gerd Jomrich, Sebastian Friedrich Schoppmann, Matthias Preusser, Aysegül Ilhan-Mutlu
ESMO Open.2020; 5(2): e000623. 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.

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Phase 1 Studies of Poziotinib, an Irreversible Pan-HER Tyrosine Kinase Inhibitor in Patients with Advanced Solid Tumors: Tae Min Kim, Keun-Wook Lee, Do-Youn Oh, Jong-Seok Lee, Seock-Ah Im, Dong-Wan Kim, Sae-Won Han, Yu Jung Kim, Tae-You Kim, Jee Hyun Kim, Hyesun Han, Woo Ho Kim, Yung-Jue Bang; Cancer Res Treat. 2018;50(3):835-842. Published online August 29, 2017; DOI: https://doi.org/10.4143/crt.2017.303

Abstract PDF Supplementary Material PubReader ePub

Purpose
Poziotinib, a pan-human epidermal growth factor receptor 2 (HER) tyrosine kinase inhibitor, has shown potent activity againstwild type of epidermal growth factorreceptor(EGFR) family kinases including EGFR, HER2, and HER4 and EGFR-mutant cells in vitro. Two phase I studies were conducted to determine the maximum tolerated dose (MTD), pharmacokinetics, safety, and antitumor activity against advanced solid tumors.
Materials and Methods
Standard 3+3 dose escalation scheme using two different dosing schedules were studied: once daily, 14-day on, and 7-day off (intermittent schedule); and once daily continuous dosing with food effect. Additional patients were enrolled in an expansion cohort.
Results
A total of 75 patients were enrolled in the two studies. The most common drug-related treatment-emergent adverse eventswere diarrhea,rash, stomatitis, pruritus, and anorexia. Doselimiting toxicities were grade 3 diarrhea in the intermittent schedule and grade 3 anorexia and diarrhea in the continuous dosing schedule. The MTDs were determined as 24 mg/day in the intermittent dosing schedule and 18 mg/day in the continuous dosing schedule. Eight (16%) and 24 (47%) of 51 evaluable patients in the intermittent schedule achieved partial response (PR) and stable disease (SD), respectively. Four (21%) and six (32%) of 19 evaluable patients in continuous dosing schedule achieved PR and SD, respectively. Patients with PR (n=7) or SD ≥ 12 weeks (n=7) had HER2 amplification (n=7; breast cancer, 5; and stomach cancer, 2) and EGFR amplification (n=1, squamous cell lung cancer).
Conclusion
Poziotinib was safe and well tolerated in patients with advanced solid tumors. It showed an encouraging activity against EGFR-mutant and HER2-amplified cancers.

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S-1–Induced Lacrimal Drainage Obstruction and Its Association with Ingredients/Metabolites of S-1 in Tears and Plasma: A Prospective Multi-institutional Study: Namju Kim, Jin Won Kim, Je-Hyun Baek, Jin-Soo Kim, Ho-Kyung Choung, Tae-Yong Kim, Kyung-Hun Lee, Yung-Jue Bang, Sang In Khwarg, Sang-Hoon Ahn, Do Joong Park, Hyung-Ho Kim, Jae-Yong Chung, Soyeon Ahn, Keun-Wook Lee; Cancer Res Treat. 2018;50(1):30-39. Published online February 27, 2017; DOI: https://doi.org/10.4143/crt.2016.569

Abstract PDF Supplementary Material PubReader ePub

Purpose
This prospective study was conducted to determine the incidence of lacrimal drainage obstruction (LDO) during S-1 chemotherapy and evaluate the association between the development of LDO and the concentrations of ingredients/metabolites of S-1 in tears and plasma.
Materials and Methods
A total of 145 patients with gastric cancer who received adjuvant S-1 therapy were enrolled. Ophthalmologic examinations were performed regularly during S-1 chemotherapy. Concentrations of tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP), and 5-fluorouracil at steady-state trough level were measured in both tears and plasma.
Results
Fifty-three patients (37%) developed LDO. The median time to the onset of LDO was 10.9 weeks, and LDO developed most frequently in the nasolacrimal duct. Univariable analyses revealed that an older age (≥ 70 years), creatinine clearance rate (Ccr) < 80 mL/min, 5-fluorouracil concentration in plasma ≥ 22.3 ng/mL (median), CDHP concentration in plasma ≥ 42.0 ng/mL (median), and tegafur concentration in tears ≥ 479.2 ng/mL (median) were related to increased development of LDO. Multivariable analysis indicated that a high plasma 5-fluorouracil concentration was predictive of increased development of LDO (hazard ratio, 2.02; p=0.040), along with older age and decreased Ccr. Patients with LDO also developed S-1–related non-hematologic toxicity more frequently than those without LDO (p=0.016).
Conclusion
LDO is a frequent adverse event during S-1 chemotherapy. An older age, decreased Ccr, and high plasma 5-fluorouracil concentration were found to be independent risk factors for LDO. The high incidence of LDO warrants regular ophthalmologic examination and early intervention in patients receiving S-1 therapy.

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Ocular complication induced by anticancer drug S-1: association with drug concentrations in tears
Masakazu Yamada, Tomoyuki Kamao, Atsushi Shiraishi, Jo Sakai, Yuichi Ohashi, Masashi Mimura, Yoshitsugu Inoue, Kazuyoshi Ohtomo, Tai-ichiro Chikama, Chika Miyazaki, Yuka Hosotani
Japanese Journal of Ophthalmology.2025;[Epub] CrossRef
Influenza A Virus Utilizes the Nasolacrimal System to Establish Respiratory Infection after Ocular Exposure in the Swine Model
Shubin Li, Xuebin Peng, MinJie Wang, Wenqian Wang, Yuye Liu, Qian Yang, Makoto Ozawa
Transboundary and Emerging Diseases.2024;[Epub] CrossRef
Nasolacrimal Duct Obstruction in the Patients Receiving Treatment for Cancer
Vasily D. Yartsev, Eugenia L. Atkova
International Ophthalmology Clinics.2023; 63(3): 137. CrossRef
Obstrução lacrimal pós-tratamento oncológico: revisão de literatura
Camilla Duarte Silva, Fabricio Lopes da Fonseca, Juliana Mika Kato, Suzana Matayoshi
Revista Brasileira de Oftalmologia.2022;[Epub] CrossRef
A Case of Nasolacrimal Duct Obstruction During S-1 Treatment For Breast Cancer
Hisataka Ominato, Michihisa Kono, Hidekiyo Yamaki, Takumi Kumai, Miki Takahara, Akihiro Katada, Tatsuya Hayashi
Practica Oto-Rhino-Laryngologica.2022; 115(6): 503. CrossRef
Corneal nerve changes following treatment with neurotoxic anticancer drugs
Jeremy Chung Bo Chiang, David Goldstein, Susanna B. Park, Arun V. Krishnan, Maria Markoulli
The Ocular Surface.2021; 21: 221. CrossRef
The impact of anticancer drugs on the ocular surface
Jeremy Chung Bo Chiang, Ilyanoon Zahari, Maria Markoulli, Arun V. Krishnan, Susanna B. Park, Annalese Semmler, David Goldstein, Katie Edwards
The Ocular Surface.2020; 18(3): 403. CrossRef
Pharmacokinetics of S-1 monotherapy in plasma and in tears for gastric cancer patients
Hirofumi Yasui, Takeshi Kawakami, Hiroya Kashiwagi, Keita Mori, Katsuhiro Omae, Jun Kasai, Kunihiro Yoshisue, Masahiro Kawahira, Takahiro Tsushima, Nozomu Machida, Akira Fukutomi, Ken Yamaguchi
International Journal of Clinical Oncology.2019; 24(6): 660. CrossRef

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A Multicenter Randomized Phase II Study of Docetaxel vs. Docetaxel Plus Cisplatin vs. Docetaxel Plus S-1 as Second-Line Chemotherapy in Metastatic Gastric Cancer Patients Who Had Progressed after Cisplatin Plus Either S-1 or Capecitabine: Keun-Wook Lee, Bum Jun Kim, Mi-Jung Kim, Hye Sook Han, Jin Won Kim, Young Iee Park, Sook Ryun Park; Cancer Res Treat. 2017;49(3):706-716. Published online October 18, 2016; DOI: https://doi.org/10.4143/crt.2016.216

Abstract PDF PubReader ePub

Purpose
This study evaluated the re-challenge of S-1 or cisplatin in combination with docetaxel in metastatic gastric cancer (MGC) that had progressed on a cisplatin plus either S-1 or capecitabine regimen.
Materials and Methods
Patients with progressive disease after first-line cisplatin plus S-1 or capecitabine were randomized to receive 3-week cycles of docetaxel 75 mg/m² intravenously (IV) on D1 (D), docetaxel 60 mg/m² IV plus cisplatin 60 mg/m² IV on D1 (DC), or docetaxel 60 mg/m² IV D1 plus oral S-1 30 mg/m² twice a day on D1-14 (DS).
Results
Seventy-two patients were randomized to the D (n=23), DC (n=24), or DS (n=25) group. The confirmed response rate was 4.3% (95% confidence interval [CI], 0% to 12.6%), 4.3% (95% CI, 0% to 12.6%), and 8.7% (95% CI, 0% to 20.2%) for the D, DC, and DS groups, respectively. Compared to the D arm, the DS arm had a better progression-free survival (2.7 months vs. 1.3 months, p=0.034) without any deterioration in safety or quality of life, whereas the DC arm had a similar progression-free survival (1.8 months vs. 1.3 months, p=0.804) and poorer overall survival (5.6 months vs. 10.0 months, p=0.035).
Conclusion
A re-challenge with S-1, but not cisplatin, in combination with docetaxel has potential anticancer benefits over docetaxel alone in MGC with progression after prior cisplatin plus S-1 or capecitabine.

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Yulia D’yachkova, Astra M. Liepa, Rajat Goel, Veronika Earley-Valovic, Abby Paine, Palvi Gupta, Kaisa Taipale
Journal of Gastrointestinal Cancer.2025;[Epub] CrossRef
Efficacy and safety of docetaxel plus S-1-based therapy in gastric cancer: a quantitative evidence synthesis of randomized controlled trials
Hui-Fen Lv, Li-Feng Qin, Rui-Zhi Ran, Xue-Ping Jiang, Fang-Yu Zhao, Bo Li
Frontiers in Pharmacology.2024;[Epub] CrossRef
Clinical Outcomes for Previously Treated Patients with Advanced Gastric or Gastroesophageal Junction Cancer: A Systematic Literature Review and Meta-Analysis
Lauren A. Abderhalden, Ping Wu, Mayur M. Amonkar, Brian M. Lang, Sukrut Shah, Fan Jin, Andrew M. Frederickson, Ali Mojebi
Journal of Gastrointestinal Cancer.2023; 54(4): 1031. CrossRef
Platinum-Based Chemotherapy ‘Rechallenge’ in Advanced Non-ovarian Solid Malignancies
J. Hack, S.J. Crabb
Clinical Oncology.2022; 34(8): e329. CrossRef
Systematic review of health-related quality of life (HRQoL) issues associated with gastric cancer: capturing cross-cultural differences
Alison Rowsell, Samantha C. Sodergren, Vassilios Vassiliou, Anne-Sophie Darlington, Marianne G. Guren, Bilal Alkhaffaf, Chantelle Moorbey, Kristopher Dennis, Mitsumi Terada
Gastric Cancer.2022; 25(4): 665. CrossRef
Considerations on the mechanics and sample sizes for early trials of targeted agents and immunotherapy in oncology
Elisabeth Coart, Everardo D. Saad
Expert Review of Precision Medicine and Drug Development.2021; 6(4): 271. CrossRef
Toward a Treatment Sequencing Strategy: A Systematic Review of Treatment Regimens in Advanced Gastric Cancer/Gastroesophageal Junction Adenocarcinoma
Daniel V. Catenacci, Joseph Chao, Kei Muro, Salah Eddin Al-Batran, Samuel J. Klempner, Zev A. Wainberg, Manish A. Shah, Sun Young Rha, Atsushi Ohtsu, Astra M. Liepa, Holly Knoderer, Anindya Chatterjee, Eric Van Cutsem
The Oncologist.2021; 26(10): e1704. CrossRef
Salvage systemic therapy for advanced gastric and oesophago-gastric junction adenocarcinoma
Yoko Tomita, Max Moldovan, Rachael Chang Lee, Amy HC Hsieh, Amanda Townsend, Timothy Price
Cochrane Database of Systematic Reviews.2020;[Epub] CrossRef
Results of the use of ramucirumab in combination with irinotecan and fluoropyrimidines in the second-line chemotherapy for disseminated gastric cancer
N. S. Besova, T. A. Titova, D. L. Stroyakovsky, E. V. Perminova, S. G. Bagrova, E. S. Obarevich, V. A. Gorbunova, E. V. Artamonova, I. S. Stilidi
Medical Council.2019; (10): 100. CrossRef
Docetaxel, cisplatin, and 5-fluorouracil compared with epirubicin, cisplatin, and 5-fluorouracil regimen for advanced gastric cancer: A systematic review and meta-analysis
Bo Li, Lian Chen, Hong-Liang Luo, Feng-Ming Yi, Yi-Ping Wei, Wen-Xiong Zhang
World Journal of Clinical Cases.2019; 7(5): 600. CrossRef
A Bayesian Network Meta-Analysis for Identifying the Optimal Taxane-Based Chemotherapy Regimens for Treating Gastric Cancer
Dan Zhang, Jia-Rui Wu, Xiao-Jiao Duan, Kai-Huan Wang, Yi Zhao, Meng-Wei Ni, Shu-Yu Liu, Xiao-Meng Zhang, Bing Zhang
Frontiers in Pharmacology.2019;[Epub] CrossRef
Systemic therapy for previously treated advanced gastric cancer: A systematic review and network meta-analysis
Ji Cheng, Ming Cai, Xiaoming Shuai, Jinbo Gao, Guobin Wang, Kaixiong Tao
Critical Reviews in Oncology/Hematology.2019; 143: 27. CrossRef
Quality of Life During Palliative Systemic Therapy for Esophagogastric Cancer: Systematic Review and Meta-Analysis
Jessy Joy van Kleef, Emil ter Veer, Héctor G van den Boorn, Sandor Schokker, Lok Lam Ngai, Mariska J Prins, Nadia Haj Mohammad, Lonneke V van de Poll-Franse, Aeilko H Zwinderman, Martijn G H van Oijen, Mirjam A G Sprangers, Hanneke W M van Laarhoven
JNCI: Journal of the National Cancer Institute.2019;[Epub] CrossRef

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Prospective Study on the Incidence of Postoperative Venous Thromboembolism in Korean Patients with Colorectal Cancer: Eunyoung Lee, Sung-Bum Kang, Sang Il Choi, Eun Ju Chun, Min Jeong Kim, Duck-Woo Kim, Heung-Kwon Oh, Myong Hoon Ihn, Jin Won Kim, Soo-Mee Bang, Jeong-Ok Lee, Yu Jung Kim, Jee Hyun Kim, Jong Seok Lee, Keun-Wook Lee; Cancer Res Treat. 2016;48(3):978-989. Published online November 17, 2015; DOI: https://doi.org/10.4143/crt.2015.311

Abstract PDF PubReader ePub

Purpose
Pharmacologic thromboprophylaxis is routinely recommended for Western cancer patients undergoing major surgery for prevention of venous thromboembolism (VTE). However, it is uncertainwhetherroutine administration of pharmacologic thromboprophylaxis is necessary in all Asian surgical cancer patients. This prospective study was conducted to examine the incidence of and risk factors for postoperative VTE in Korean colorectal cancer (CRC) patients undergoing major abdominal surgery. Materials and Methods This study comprised two cohorts, and none of patients received perioperative pharmacologic thromboprophylaxis. In cohort A (n=400), patients were routinely screened for VTE using lower-extremity Doppler ultrasonography (DUS) on postoperative days 5-14. In cohort B (n=148), routine DUS was not performed, and imaging was only performed when there were symptoms or signs that were suspicious for VTE. The primary endpoint was the VTE incidence at 4 weeks postoperatively in cohort A.
Results
The postoperative incidence of VTE was 3.0% (n=12) in cohort A. Among the 12 patients, eight had distal calf vein thromboses and one had symptomatic thrombosis. Age ≥ 70 years (odds ratio [OR], 5.61), ≥ 2 comorbidities (OR, 13.42), and white blood cell counts of > 10,000/μL (OR, 17.43) were independent risk factors for postoperative VTE (p < 0.05). In cohort B, there was one case of VTE (0.7%). Conclusion The postoperative incidence of VTE, which included asymptomatic cases, was 3.0% in Korean CRC patients who did not receive pharmacologic thromboprophylaxis. Perioperative pharmacologic thromboprophylaxis should be administered to Asian CRC patients on a riskstratified basis.

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Hsuan-Yu Lin, Ting-Ming Huang, Ching-Yeh Lin, Ming-Ching Shen
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Hyung Jin Cho, In Kyu Lee, Yoon Suk Lee, Sang Seob Yun, Sun Cheol Park, Jang Yong Kim, Chul Seung Lee
European Journal of Surgical Oncology.2022; 48(6): 1384. CrossRef
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Joshua W. Hayes, Éanna J. Ryan, Patrick A. Boland, Ben Creavin, Michael E. Kelly, David Beddy
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European guidelines on perioperative venous thromboembolism prophylaxis
Sibylle Kozek-Langenecker, Christian Fenger-Eriksen, Emmanuel Thienpont, Giedrius Barauskas
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The identification of risk factors for venous thromboembolism in gastrointestinal oncologic surgery
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Phase I Study of CKD-516, a Novel Vascular Disrupting Agent, in Patients with Advanced Solid Tumors: Do-Youn Oh, Tae-Min Kim, Sae-Won Han, Dong-Yeop Shin, Yun Gyoo Lee, Keun-Wook Lee, Jee Hyun Kim, Tae-You Kim, In-Jin Jang, Jong-Seok Lee, Yung-Jue Bang; Cancer Res Treat. 2016;48(1):28-36. Published online February 23, 2015; DOI: https://doi.org/10.4143/crt.2014.258

Abstract PDF PubReader ePub

Purpose
CKD-516 is a newly developed vascular disrupting agent. This phase I dose-escalation study of CKD-516 was conducted to determine maximum-tolerated dose (MTD), safety, pharmacokinetics, and preliminary antitumor efficacy in patients with advanced solid tumors. Materials and Methods Patients received CKD-516 intravenously on D1 and D8 every 3 weeks, in a standard 3+3 design. Safety was evaluated by National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.02 and response was assessed by Response Evaluation Criteria in Solid Tumor ver. 1.1.
Results
Twenty-three patients were treated with CKD-516 at seven dosing levels: 1 mg/m2/day (n=3), 2 mg/m2/day (n=3), 3.3 mg/m2/day (n=3), 5 mg/m2/day (n=3), 7 mg/m2/day (n=3), 9 mg/m2/day (n=6), and 12 mg/m2/day (n=2). Mean age was 54 and 56.5% of patients were male. Two dose-limiting toxicities, which were both grade 3 hypertension, were observed in two patients at 12 mg/m2/day. The MTD was determined as 12 mg/m2/day. Most common adverse events were gastrointestinal adverse events (diarrhea, 34.8% [30.4% grade 1/2, 13.0% grade 3]; nausea, 21.7% [all grade 1/2]; vomiting, 21.7% [all grade 1/2]), myalgia (17.4%, all grade 1/2), and abdominal pain (21.7% [21.7% grade 1/2, 4.3% grade 3]). The pharmacokinetic study showed the dose-linearity of all dosing levels. Among 23 patients, six patients (26.1%) showed stable disease. Median progression-free survival was 39 days (95% confidence interval, 37 to 41 days). Conclusion This study demonstrates feasibility of CKD-516, novel vascular disrupting agent, in patients with advanced solid tumor. MTD of CKD-516 was defined as 12 mg/m2/day on D1 and D8 every 3 weeks.

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Phase I Study of Axitinib in Combination with Cisplatin and Capecitabine in Patients with Previously Untreated Advanced Gastric Cancer: Do-Youn Oh, Toshihiko Doi, Kuniaki Shirao, Keun-Wook Lee, Sook Ryun Park, Ying Chen, Liqiang Yang, Olga Valota, Yung-Jue Bang; Cancer Res Treat. 2015;47(4):687-696. Published online February 12, 2015; DOI: https://doi.org/10.4143/crt.2014.225

Abstract PDF PubReader ePub

Purpose
This phase I trial evaluated the question of whether the standard starting dose of axitinib could be administered in combination with therapeutic doses of cisplatin/capecitabine in patients with previously untreated advanced gastric cancer, and assessed overall safety, pharmacokinetics, and preliminary antitumor activity of this combination.
Materials and Methods
Patients in dose level (DL) 1 received axitinib 5 mg twice a day (days 1 to 21) with cisplatin 80 mg/m2 (day 1) and capecitabine 1,000 mg/m2 twice a day (days 1 to 14) in 21-day cycles. Maximum tolerated dose (MTD) was the highest dose at which ≤ 30% of the first 12 patients experienced a dose-limiting toxicity (DLT) during cycle 1. Ten additional patients were enrolled and treated at the MTD in order to obtain additional safety and pharmacokinetic data.
Results
Three DLTs occurred during cycle 1 in three (25%) of the first 12 patients: ruptured abdominal aortic aneurysm, acute renal failure, and > 5 consecutive days of missed axitinib due to thrombocytopenia. DL1 was established as the MTD, since higher DL cohorts were not planned. Common grade 3/4 non-hematologic adverse events in 22 patients treated at DL1 included hypertension (36.4%) and decreased appetite and stomatitis (18.2% each). Cisplatin/capecitabine slightly increased axitinib exposure; axitinib decreased capecitabine and 5-fluorouracil exposure. Eight patients (36.4%) each had partial response or stable disease. Median response duration was 9.1 months; median progression-free survival was 3.8 months.
Conclusion
In patients with advanced gastric cancer, standard doses of axitinib plus therapeutic doses of cisplatin and capecitabine could be administered in combination. Adverse events were manageable.

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Heng Yun, Fangde Dong, Xiaoqin Wei, Xinyong Yan, Ronglong Zhang, Xiuyu Zhang, Yulin Wang
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Cuncan Deng, Guofei Deng, Hongwu Chu, Songyao Chen, Xiancong Chen, Xing Li, Yulong He, Chunhui Sun, Changhua Zhang
Frontiers in Immunology.2023;[Epub] CrossRef
Early TP53 Alterations Shape Gastric and Esophageal Cancer Development
Pranshu Sahgal, Brandon M. Huffman, Deepa T. Patil, Walid K. Chatila, Rona Yaeger, James M. Cleary, Nilay S. Sethi
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High ELK3 Expression is Associated with the VEGF-C/VEGFR-3 Axis and Gastric Tumorigenesis and Enhances Infiltration of M2 Macrophages
Wang Dazhi, Jiao Zheng, Ren Chunling
Future Medicinal Chemistry.2020; 12(24): 2209. CrossRef
RETRACTED: Long non-coding RNA LINC00978 promotes cell proliferation and tumorigenesis via regulating microRNA-497/NTRK3 axis in gastric cancer
Ju-Yuan Bu, Wei-Ze Lv, Yi-Feng Liao, Xiao-Yu Xiao, Bao-Jun Lv
International Journal of Biological Macromolecules.2019; 123: 1106. CrossRef
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Lin Yang, Yanan Yu, Qi Zhang, Xiaoyu Li, Cuiping Zhang, Tao Mao, Siliang Liu, Zibin Tian
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Claudia Arena, Giuseppe Troiano, Alfredo De Lillo, Nunzio F. Testa, Lorenzo Lo Muzio
BioMed Research International.2018; 2018: 1. CrossRef
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Li-Tzong Chen, Do-Youn Oh, Min-Hee Ryu, Kun-Huei Yeh, Winnie Yeo, Roberto Carlesi, Rebecca Cheng, Jongseok Kim, Mauro Orlando, Yoon-Koo Kang
Cancer Research and Treatment.2017; 49(4): 851. CrossRef
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Mauricio P. Pinto, Gareth I. Owen, Ignacio Retamal, Marcelo Garrido
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Cisplatin-Based Chemotherapy Is a Strong Risk Factor for Thromboembolic Events in Small-Cell Lung Cancer: Yun-Gyoo Lee, Eunyoung Lee, Inho Kim, Keun-Wook Lee, Tae Min Kim, Se-Hoon Lee, Dong-Wan Kim, Dae Seog Heo; Cancer Res Treat. 2015;47(4):670-675. Published online January 2, 2015; DOI: https://doi.org/10.4143/crt.2014.045

Abstract PDF PubReader ePub

Purpose
Cisplatin-associated arterial and venous thromboembolic events (TEEs) are becoming an increasing concern. In patients with small-cell lung cancer (SCLC) who are treated using cisplatin-based chemotherapy, we assume that the overall risk of TEEs is high. However, cisplatin-associated vascular toxicity in patients with SCLC has been overlooked to date. The aim of this study was to determine the incidence of TEEs in patients with SCLC and to analyze the predictors for TEE occurrence. Materials and Methods We retrospectively analyzed 277 patients who received chemotherapy for SCLC between 2006 and 2012. As the influence of chemotherapy on TEE occurrence developed after its initiation, a time-dependent Cox regression analysis was used to estimate the significant predictors for TEE. Results Among the 277 patients, 30 patients (11%) developed a TEE. The 3-month, 6-month, and 1-year cumulative incidences of TEEs were 5.0%, 9.1%, and 10.2%, respectively. Of 30 total TEEs, 22 (73%) occurred between the time of initiation and 4 weeks after the last dose of platinum-based chemotherapy. Approximately 218 patients (79%) received cisplatin-based chemotherapy. In multivariate analysis, cisplatin-based chemotherapy was an independent risk factor for TEE occurrence (hazard ratio [HR], 4.36; p=0.05). Variables including smoking status (common HR, 2.14; p=0.01) and comorbidity index (common HR, 1.60; p=0.05) also showed significant association with TEE occurrence. Conclusion The 1-year cumulative incidence of TEE is 10.2% in Asian patients with SCLC. Cisplatinbased chemotherapy in SCLC might be a strong predictor for the risk of TEE.

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Seratrodast platinum(iv) hybrids efficiently inhibit cancer-related thrombosis and metastasis phenotype in vitro and in vivo
Xue-Qing Song, Yi-Xin Ding, Yu-Hang Zhang, Qing Xu, Xiaofeng Xie, Yali Song, Longfei Li
Inorganic Chemistry Frontiers.2023; 10(22): 6596. CrossRef
Analysis of thromboembolic events in head and neck cancer patients who underwent concurrent chemoradiotherapy with cisplatin
Hundo Cho, Jin-Hyuk Choi, Seok Yun Kang, Hyun Woo Lee, Yong Won Choi, Tae-Hwan Kim, Mi Sun Ahn, Chul-Ho Kim, Yoo Seob Shin, Jeon Yeob Jang, Young-Taek Oh, Jaesung Heo, Seung Soo Sheen
The Korean Journal of Internal Medicine.2022; 37(3): 653. CrossRef
Analysis of thromboembolic events in patients with non-small cell lung cancer who received adjuvant chemotherapy: single-center real-world data
Tae-Hwan Kim, Yong Won Choi, Hyun Woo Lee, Seok Yun Kang, Heejun Son, Jin-Hyuk Choi, Mi Sun Ahn, Seung-Soo Sheen
Scientific Reports.2022;[Epub] CrossRef
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Yukiko Ochiai, Marie Tsunogae, Masayuki Ueda
Internal Medicine.2021; 60(6): 945. CrossRef
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Yu-Dong Li, Hai-Dong Li, Shu-Xin Zhang
International Angiology.2020;[Epub] CrossRef
Evaluation of Biomarkers for the Prediction of Venous Thromboembolism in Ambulatory Cancer Patients
Ruth Maria Schorling, Christian Pfrepper, Thomas Golombek, Chiara Alessandra Cella, Nerea Muñoz-Unceta, Roland Siegemund, Christoph Engel, Sirak Petros, Florian Lordick, Maren Knödler
Oncology Research and Treatment.2020; 43(9): 414. CrossRef
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Takeshi Yagyu, Maiko Naito, Masahiro Kumada, Tsutomu Nakagawa
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Silvia Riondino, Patrizia Ferroni, Fabio Massimo Zanzotto, Mario Roselli, Fiorella Guadagni
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Michał Ząbczyk, Grzegorz Królczyk, Grzegorz Czyżewicz, Krzysztof Plens, Shannon Prior, Saulius Butenas, Anetta Undas
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Evangelos Dimakakos, Konstantinos Livanios, Ioannis Gkiozos, Adriani Charpidou, Eleutheria Ntalakou, llias Kainis, Konstantinos Syrigos
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p21-Activated Kinase 4 (PAK4) as a Predictive Marker of Gemcitabine Sensitivity in Pancreatic Cancer Cell Lines: Sung-Ung Moon, Jin Won Kim, Ji Hea Sung, Mi Hyun Kang, Se-Hyun Kim, Hyun Chang, Jeong-Ok Lee, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Jong Seok Lee; Cancer Res Treat. 2015;47(3):501-508. Published online November 24, 2014; DOI: https://doi.org/10.4143/crt.2014.054

Abstract PDF PubReader ePub

Purpose
p21-activated kinases (PAKs) are involved in cytoskeletal reorganization, gene transcription, cell proliferation and survival, and oncogenic transformation. Therefore, we hypothesized that PAK expression levels could predict the sensitivity of pancreatic cancer cells to gemcitabine treatment, and PAKs could be therapeutic targets.
Materials and Methods
Cell viability inhibition by gemcitabine was evaluated in human pancreatic cancer cell lines (Capan-1, Capan-2, MIA PaCa-2, PANC-1, Aspc-1, SNU-213, and SNU-410). Protein expression and mRNA of molecules was detected by immunoblot analysis and reverse transcription polymerase chain reaction. To define the function of PAK4, PAK4 was controlled using PAK4 siRNA.
Results
Capan-2, PANC-1, and SNU-410 cells were resistant to gemcitabine treatment. Immunoblot analysis of signaling molecules reported to indicate gemcitabine sensitivity showed higher expression of PAK4 and lower expression of human equilibrative nucleoside transporter 1 (hENT1), a well-known predictive marker for gemcitabine activity, in the resistant cell lines. Knockdown of PAK4 using siRNA induced the upregulation of hENT1. In resistant cell lines (Capan-2, PANC-1, and SNU-410), knockdown of PAK4 by siRNA resulted in restoration of sensitivity to gemcitabine.
Conclusion
PAK4 could be a predictive marker of gemcitabine sensitivity and a potential therapeutic target to increase gemcitabine sensitivity in pancreatic cancer.

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Kajal Kaliya, Neha Bhardwaj, Ruchika, Ankit Saneja
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Five-Year Follow-up Study of Monoclonal Gammopathy of Undetermined Significance in a Korean Elderly Urban Cohort: Yun-Gyoo Lee, Soo-Mee Bang, Jeong-Ok Lee, Jin Won Kim, Keun-Wook Lee, Jee Hyun Kim, Jung Han Song, Tae-Hee Kim, Ki Woong Kim, Jong-Seok Lee; Cancer Res Treat. 2015;47(2):215-220. Published online August 29, 2014; DOI: https://doi.org/10.4143/crt.2013.262

Abstract PDF PubReader ePub

Purpose
We previously reported the prevalence of monoclonal gammopathy of undetermined significance (MGUS) to be 3.3% among an elderly Korean urban cohort recruited during 2005-2006. Here, we report a 5-year follow-up study of the previously identified MGUS cohort.
Materials and Methods
The 680 participants from the initial cohort were followed-up for a median of 5 years. Sera were collected between 2010 and 2011. Two-step screening was performed with standard serum electrophoresis followed by immunofixation and determination of the serum concentration of monoclonal-protein (M-protein).
Results
Of the 680 participants (21 with MGUS), 348 (51%) agreed to participate in the follow-up study and 10 were found to have MGUS. Among the 21 MGUS patients initially identified, nine were followed-up, six had persistent M-protein, and one patient had progressed to multiple myeloma (progression rate, 1.0%/yr). The M-protein disappeared in the remaining two individuals. Among the 339 participants without MGUS who were followed-up, four developed an M-protein. There was no significant difference in survival with respect to the presence of MGUS (p=0.66).
Conclusion
The 5-year follow-up data show that the natural clinical course of MGUS in Korea is similar to that in Western countries. MGUS was not associated with an increased risk of death over the 5-year study period.

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