Cancer Research and Treatment

Original Articles

Associations between Smoking, Opioid Analgesic Use, and Risk For Chemical Coping in Korean Patients with Advanced Cancer: Eun Hee Jung, Yu Jung Kim, Rony Dev, Koung Jin Suh, Ji-Won Kim, Se Hyun Kim, Jin Won Kim, Keun-Wook Lee, Jee Hyun Kim, Jong Seok Lee, Eduardo Bruera; Received September 20, 2025 Accepted February 2, 2026 Published online February 3, 2026; DOI: https://doi.org/10.4143/crt.2025.1034 [Accepted]

Abstract PDF: Purpose
We investigated the associations between smoking, pain expression, opioid use, substance use behaviors, coping strategies, and risk of chemical coping in Korean patients with advanced cancer.
Materials and Methods
In this prospective study, 240 patients were enrolled. Demographic and clinical information were obtained from medical records. Smoking status, symptom burden by the Edmonton Symptom Assessment System (ESAS), the Cut down/Annoyed/Guilty/Eye-opener (CAGE) alcoholism questionnaire results, morphine equivalent daily dose (MEDD), tranquilizers and coffee use, coping strategies, and physician-assessed risk of chemical coping and somatization were assessed using questionnaires and interviews.
Results
Of the 240 patients, 49 (20.4%) were current smokers, 104 (43.3%) were former smokers, and 87 (36.3%) were never-smokers. 161 were male (67.1%); 89.4% (144/161) of these men were current or former smokers, while 88.6% (70/79) of women were never-smokers (p<0.001). ESAS pain scores did not differ by smoking status (3.0 vs. 2.9 vs. 2.7, p=0.480), but current smokers had higher MEDD (63.5 mg/day vs. 25.1 mg/day vs. 22.3 mg/day, p=0.015). Current smokers were more often CAGE-positive (32.7% vs. 16.3% vs. 2.3%, p<0.001), heavy coffee drinkers (24.5% vs. 12.5% vs. 0%, p<0.001) and showed a greater physician-assessed risk of chemical coping (26.5% vs. 8.7% vs. 13.8%, p=0.015).
Conclusion
Among Korean patients with advanced cancer, current smokers were more likely to use higher doses of opioids, have positive CAGE results, and drink more coffee. Close monitoring and appropriate management for the possibility of chemical coping or non-medical opioid use will be important in these patients.

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Zolbetuximab Plus Chemotherapy as First-Line Treatment in Patients with Claudin 18.2-Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma: Korean Population Subgroup—Combined Efficacy and Safety Analysis from SPOTLIGHT and GLOW: Keun-Wook Lee, Sang Cheul Oh, Jong Gwang Kim, Sun Jin Sym, Byoung Yong Shim, Seok Yun Kang, In-Ho Kim, Jwa Hoon Kim, Hong Jae Chon, Sang-Hee Cho, Eun-Kee Song, Do-Youn Oh, Jin-Soo Kim, Young Iee Park, Won Ki Kang, Hyung-Don Kim, Janise Lee, Miri Yi, Min-Hee Ryu; Received August 28, 2025 Accepted December 4, 2025 Published online December 5, 2025; DOI: https://doi.org/10.4143/crt.2025.935 [Accepted]

Abstract PDF: Purpose
The phase 3 SPOTLIGHT and GLOW trials, in patients with claudin 18 isoform 2–positive, human epidermal growth factor receptor 2–negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma, demonstrated statistically significant and clinically meaningful improvement in progression-free survival (PFS) and overall survival (OS) with first-line zolbetuximab plus chemotherapy versus placebo plus chemotherapy. This analysis evaluated efficacy and safety in the Korean subgroup from SPOTLIGHT and GLOW.
Materials and Methods
Patients were randomized 1:1 to receive zolbetuximab plus chemotherapy or placebo plus chemotherapy (mFOLFOX6 [modified folinic acid, 5-fluorouracil, and oxaliplatin] or CAPOX [capecitabine and oxaliplatin]). Primary endpoint was PFS, assessed per RECIST v1.1 by independent review committee. Other efficacy and safety parameters were assessed.
Results
The Korean subgroup consisted of 49 patients in the zolbetuximab group and 47 in the placebo group. Median PFS (95% confidence interval [CI]) was 12.3 months (7.3-15.3), and median OS was 30.5 months (16.1-45.5) with zolbetuximab versus 8.1 months (4.2-10.4) and 15.8 months (11.8-19.7) with placebo, respectively. Most common TEAEs in patients who received zolbetuximab versus placebo were nausea (79.6% vs. 53.2%), vomiting (55.1% vs. 21.3%), and decreased appetite (53.1% vs. 23.4%). Treatment-related TEAEs led to discontinuation of zolbetuximab and placebo in 4.1% and 2.1% of patients, respectively.
Conclusion
Zolbetuximab plus chemotherapy demonstrated favorable PFS and OS versus placebo plus chemotherapy in the Korean subgroup, with numerically greater efficacy compared with the overall pooled population. This may be potentially attributable to low rates of zolbetuximab discontinuation and toxicity management.

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Clinicopathological Factors Influencing PD-L1 Expression and the Effect of Immune Checkpoint Inhibitors on Survival Outcomes in Patients with Gastric Cancer Depending on Sex in a Tertiary Hospital in South Korea: Jeong hwan Lee, Nayoung Kim, Ji-Hyun Kim, Hyeon Jeong Oh, Yeejin Kim, Yonghoon Choi, Hyemin Jo, Ho-Kyoung Lee, Jinju Choi, Yu Kyung Jun, Hyuk Yoon, Cheol Min Shin, Young Soo Park, Dong Ho Lee, Hye Seung Lee, So Hyun Kang, Young Suk Park, Sang-Hoon Ahn, Yun-Suhk Suh, Do Joong Park, Hyung Ho Kim, Ji-Won Kim, Jin Won Kim, Keun-Wook Lee, Won Chang, Yoon Jin Lee, Kyoung Ho Lee, Young Hoon Kim, Soyeon Ahn; Received January 31, 2025 Accepted August 5, 2025 Published online August 13, 2025; DOI: https://doi.org/10.4143/crt.2025.126 [Epub ahead of print]

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Purpose
Programmed cell death ligand-1 (PD-L1) negatively regulates T-cell activation, and exhibits sex-based differences in expression and immune responses. This study investigated sex-related differences in clinicopathological factors influencing PD-L1 expression and the effect of immune checkpoint inhibitors (ICIs) on survival in gastric cancer (GC) patients in South Korea.
Materials and Methods
We analyzed a prospective cohort of 468 GC patients who underwent PD-L1 immunohistochemistry. Age, tumor characteristics, molecular features, and survival outcomes were compared by sex. Multivariate analyses, including Cox proportional hazards modeling with an interaction term for sex, were performed.
Results
Among 468 patients, 280 (59.8%) were PD-L1 positive. In the overall cohort, PD-L1 positivity was significantly associated with Epstein-Barr virus (EBV) infection (odds ratio [OR], 7.46; p < 0.001), antral location of GC (OR, 1.84; p=0.027), and macrosatellite instability–high (MSI-H) (OR, 5.04; p=0.027). Diffuse-type histology was inversely associated (OR, 0.22; p=0.041). In males, EBV (OR, 36.27) and antral location (OR, 2.38) were significant. In females, only MSI-H was significant (OR, 11.63). ICI-containing therapy significantly improved survival in males (p=0.012) but not in females (p=0.415). Cox regression showed a survival benefit from ICIs (hazard ratio, 0.70; p=0.080), with a borderline-significant interaction by sex (p=0.073).
Conclusion
PD-L1 expression and therapeutic efficacy of ICIs differ by sex in GC. EBV infection and antral tumor location were independent factors in males, while MSI-H status was significant in females. These findings highlight the importance of sex-based immunobiology in tailoring GC treatment strategies.

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Prognostic implications of PD-L1 expression in gastric cancer: systematic review and meta-analysis of studies published between 2018 and 2025
Gulnaz Yessultanova, Zhanat Komekbay, Indira Karibayeva, Anar Tulyayeva, Nurgul Kereyeva, Aigul Zhumasheva, Lunara Ishimova
BMC Cancer.2026;[Epub] CrossRef

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Nivolumab Plus Chemotherapy Versus Placebo Plus Chemotherapy in Korean Patients with HER2-Negative, Untreated, Unresectable Advanced or Recurrent Gastric or Gastroesophageal Junction Cancer: Subgroup Analysis of a Randomized, Multicenter, Double-Blind Phase 3 Trial (ATTRACTION-4): Yoon-Koo Kang, Min-Hee Ryu, Do-Youn Oh, Sang Cheul Oh, Sun Young Rha, Keun-Wook Lee, Ik Joo Chung, Sung Yong Oh, Sun Jin Sym, Won Ki Kang, Jong Gwang Kim, Byoung Yong Shim, In-Ho Kim, Jin Young Kim, Eun-Kee Song, Hyo-Jin Lee, Seok Yun Kang, Dong-Hoe Koo, So Yeon Oh; Received September 13, 2024 Accepted July 1, 2025 Published online July 2, 2025; DOI: https://doi.org/10.4143/crt.2024.913 [Epub ahead of print]

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Purpose
We report the safety and efficacy of nivolumab+chemotherapy for first-line treatment of advanced or recurrent gastric or gastroesophageal junction cancer in the Korean subpopulation of the ATTRACTION-4 clinical trial.
Materials and Methods
ATTRACTION-4 (NCT02746796) was a double-blind, randomized, placebo-controlled clinical trial of patients aged ≥ 20 years with histologically confirmed unresectable advanced or recurrent gastric or gastroesophageal junction cancer. Patients received nivolumab or placebo, both combined with physician-choice chemotherapy (oxaliplatin plus oral S-1 [tegafur–gimeracil–oteracil] [SOX] or oral capecitabine [CAPOX]).
Results
Overall, 464 patients were initially screened in Korea and 291 were randomized to nivolumab+chemotherapy (total/SOX/CAPOX: 148/66/82 patients) or placebo+chemotherapy (total/SOX/CAPOX: 143/61/82 patients). Centrally assessed progression-free survival (median, 14.75 vs. 8.34 months; hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.39 to 0.73; p < 0.001), overall survival (19.7 vs. 14.9 months; HR, 0.78; 95% CI, 0.60 to 1.02; p=0.065), overall response rate (54.7% vs. 47.6%), and duration of response (16.03 vs. 9.86 months) favored nivolumab+chemotherapy vs. placebo+chemotherapy. Grade ≥ 3 treatment-related adverse events (TRAEs) (56.1% vs. 44.1%), and any-grade endocrine (9.5% vs. 4.2%), hepatic (23.0% vs. 14.7%), hypersensitivity and infusion reactions (15.5% vs. 7.0%), renal (4.1% vs. 0.7%), and skin (44.6% vs. 23.1%) TRAEs tended to be more frequent in the nivolumab+chemotherapy group.
Conclusion
These findings demonstrate the clinical benefit of nivolumab combined with chemotherapy (either SOX or CAPOX) for first-line treatment of gastric cancer/gastroesophageal junction cancer in Korean patients.

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Claudin18.2 promote gastric cancer proliferation by activating MCM2/5
Bowen Zheng, Miao Fu, Fanzhuoran Lou, Yuting He, Lingying Zhao, Xintian Huang, Xiaowen Xie, Weijuan Tan, Quan Chen, Wenqing Zhang, Yongxiang Hong, Kaiyi Rong, Yuyan Lu, Ping Zhan, Jingke Tu, Huibo Shi, Tianhui Hu, Li Xiao
Scientific Reports.2026;[Epub] CrossRef
Skin toxicity induced by chemotherapy or molecular targeted therapy combined with immune checkpoint inhibitors in Asian patients: A literature review by the Japanese Pharmacist-led Oncodermatology Study Team
Yohei Iimura, Junichi Higuchi, Akimitsu Maeda, Kazuhiro Shimomura, Hirotoshi Iihara, Hironori Fujii, Takuya Iwamoto, Yoshitaka Saito, Hisanaga Nomura, Keiko Komori, Hidenori Tokuda, Ryuta Urakawa, Tatsuya Sumiya, Ryosuke Yanai, Mariko Kono, Masaki Ihira,
International Journal of Clinical Oncology.2026; 31(6): 957. CrossRef
Overcoming diagnostic pitfalls in primary gastric squamous cell carcinoma: the imperative of adequate sampling in an elderly female patient, case report
Wanhui Dong, Li Cheng, Jing Xu, Sheng Xu, Yuling Yin, Qingming Sun, Yong Wu, Yuling Leng
Frontiers in Oncology.2025;[Epub] CrossRef

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Gastrointestinal cancer

Survival Rates of Patients with Gastric Cancer According to Age and Sex: A Large-Scale Study Using Data from 14,739 Patients: Yonghoon Choi, Nayoung Kim, Ji Hyun Kim, Hyeong Ho Jo, Hyeon Jeong Oh, Hye Seung Lee, Yu Kyung Jun, Hyuk Yoon, Cheol Min Shin, Young Soo Park, Dong Ho Lee, So Hyun Kang, Young Suk Park, Sang-Hoon Ahn, Yun-Suhk Suh, Do Joong Park, Hyung Ho Kim, Ji-Won Kim, Jin Won Kim, Keun-Wook Lee, Won Chang, Yoon Jin Lee, Kyoung Ho Lee, Young Hoon Kim; Cancer Res Treat. 2026;58(1):252-263. Published online April 16, 2025; DOI: https://doi.org/10.4143/crt.2025.149

Abstract PDF Supplementary Material PubReader ePub

Purpose
The male predominance in the incidence of gastric cancer (GC) is established; however, sex differences in the prognosis of GC remain controversial. As such, this study analyzed the prognosis of patients with GC based on age and sex.
Materials and Methods
Data from 14,739 patients diagnosed with GC at Seoul National University Bundang Hospital between 2003 and 2023 were analyzed. Baseline characteristics, histological types of GC, overall and GC-specific survival rates (age and stage stratification), and associated risk factors were analyzed.
Results
Females were significantly younger (p < 0.001) and exhibited more gastric body cancers (p < 0.001) and tumors with diffuse-type or poorly differentiated histology (p < 0.001) than males. Females exhibited an advantage over males in terms of overall survival (p=0.004), but not in GC-specific survival. However, age stratification revealed significant sex differences, that females < 50 years of age exhibited survival disadvantages (p < 0.001); however, this trend was reversed with age, and females > 60 years exhibited survival advantages (p < 0.001) for both overall and GC-specific survival. This may be explained by the lower ratio of diffuse-type GC as females age. Furthermore, in the analysis according to stage, females with stage IV disease exhibited significant survival disadvantages, with significantly younger age and a higher proportion of diffuse-type GC which exhibits aggressive features, resulting in poorer survival than in males.
Conclusion
Age and stage stratification revealed significant differences in survival between the sexes, which can be helpful for public health strategies.

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Validation of Textbook Outcome in Gastric Surgery (TOGS) for Primary Gastric Cancer in an Eastern High-Volume Center
Ludovico Carbone, Yo-Seok Cho, Min Kyu Kang, Kyoyoung Park, Jane Chungyoon Kim, Sa-Hong Kim, Jeesun Kim, Nina Rebecca Kalaw, Yoonjin Kwak, Hye Seung Lee, Seong-Ho Kong, Do Joong Park, Daniele Marrelli, Han-Kwang Yang, Franco Roviello, Hyuk-Joon Lee
Annals of Surgical Oncology.2026;[Epub] CrossRef
Age-related prognostic trends in surgically resected female lymph node-metastatic gastric cancer: insights from SEER
Bozhi Hu, Yinli Zhang, Yingjiang Ye, Zhidong Gao, Chao Wang
International Journal of Clinical Oncology.2026;[Epub] CrossRef

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Palliative medicine

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; Cancer Res Treat. 2026;58(1):329-338. Published online March 12, 2025; DOI: https://doi.org/10.4143/crt.2025.079

Abstract PDF Supplementary Material PubReader ePub: 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 activities of daily living (100%)/instrumental activities of daily living (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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Head and Neck cancer

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; Cancer Res Treat. 2025;57(4):968-980. Published online January 31, 2025; DOI: https://doi.org/10.4143/crt.2024.1195

Abstract PDF Supplementary Material PubReader ePub

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 PIK3CAα (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) 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, overall survival (OS), and progression-free survival (PFS).
Results
From October 2017 and August 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 mutation (H1047), patients with H1047 mutation 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 mutation 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 next-generation sequencing 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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Actualités 2025 par le comité de rédaction du Bulletin du Cancer : congrès ASCO, ESMO et au-delà
Stéphane Vignot, Audrey Bellesoeur, Delphine Borchiellini, Carole Bouleuc, Romain Cohen, Alexandre de Nonneville, Frédéric Delom, Serge Evrard, Nelly Firmin, Virginie Gandemer, Mohamed Khettab, Daniel Orbach, Manuel Rodrigues, Sébastien Thureau, Marie Wis
Bulletin du Cancer.2026; 113(1): 8. CrossRef
Beyond EGFR inhibition in head and neck squamous cell carcinoma: Overcoming resistance mechanisms and novel therapeutic frontiers
Francesca Carosi, Daria Maria Filippini, Laura Fabbri, Andrea Carlini, Andrea Monte, Michela Sgarzi, Matteo Fermi, Giulia Querzoli, Donatella Romaniello, Giuseppe Mercante, Achille Tarsitano, Christophe Le Tourneau, Mattia Lauriola
Critical Reviews in Oncology/Hematology.2026; 221: 105207. CrossRef
Prognostic Biomarkers and Immunotherapeutic Insights of Circulating Tumor DNA Analysis in Advanced Esophageal Squamous Cell Carcinoma From SCRUM-MONSTAR GOZILA Substudy
Yuqing Duan, Tadayoshi Hashimoto, Taro Shibuki, Hiroya Taniguchi, Yu Sunakawa, Yoshito Komatsu, Naoki Takahashi, Yuta Sato, Kensei Yamaguchi, Tomohiro Nishina, Tomonori Nakanoko, Shogen Boku, Taroh Satoh, Hisateru Yasui, Taito Esaki, Mitsuho Imai, Takao F
JCO Precision Oncology.2026;[Epub] CrossRef
Driving progress in recurrent and metastatic head and neck cancer: the NRG Oncology perspective
Mercedes Herrera, Matthew Ward, Glenn J Hanna, Sue S Yom, Dwight Heron, Anna Spreafico
JNCI: Journal of the National Cancer Institute.2026;[Epub] CrossRef
PIK3CA Mutations: Are They a Relevant Target in Adult Diffuse Gliomas?
Ana Tomás, Marta Pojo
International Journal of Molecular Sciences.2025; 26(11): 5276. CrossRef

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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; Cancer Res Treat. 2025;57(3):709-719. Published online December 23, 2024; DOI: https://doi.org/10.4143/crt.2024.836

Abstract PDF PubReader ePub

Purpose
Tumor suppressor p53 (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 human papillomavirus–negative and non-oropharyngeal cancers. Patients with TP53 mutations exhibited shorter progression-free survival 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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Early-Onset Oral Tongue Squamous Cell Carcinoma in the Absence of Traditional Risk Factors: A Case Report with Whole-Exome Sequencing Analysis
Evgeniy Aleksiev, Darina Lyudmilova Kachakova-Yordanova, Vanyo Mitev, Martin Marinov Georgiev, Zornitsa Mihaylova
Reports.2026; 9(2): 130. CrossRef

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Hematologic malignancy

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; Cancer Res Treat. 2025;57(2):612-620. Published online September 20, 2024; DOI: https://doi.org/10.4143/crt.2024.738

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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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Myeloproliferative Neoplasms, Clonal Thrombosis, and Vascular Disease: Can Cardiology Learn from Hematology?
Jatin Thukral, Sehajnoor Kaur Khangurra, Manav Ghaie, Maneet Kaur, Pyush Moudgil, Riya Shah, Harbir Kaur, Nikhil Thukral, William H. Frishman, Wilbert S. Aronow
Cardiology in Review.2026;[Epub] CrossRef
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
Dabigatran etexilate

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Clinical and Molecular Insights of Arterial and Venous Thrombosis in Myeloproliferative Diseases—Case-Based Narrative Review
Anca Drăgan, Mădălina Găvănescu, Adrian Ştefan Drăgan, Alexandru Bardaş, Monica Dobrovie, Anca Doina Mateescu
Biomedicines.2025; 13(10): 2543. 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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Unraveling the nexus: Tumor mutational burden, PD‐L1 expression, and oncogenic alterations in non–small cell lung cancer cytology specimens
Min Dai, Francis Anthony San Lucas, Hector Alvarez, Leomar Ballester, Hui Chen, Keyur P. Patel, Asif Rashid, Shun Rao, Mark J. Routbort, Gloria Sura, Keith Sweeney, Gokce Toruner, Peng Wei, Richard Yang, Hyvan Dang, Rajyalakshmi Luthra, Sinchita Roy‐Chowd
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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
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Marco Sposito, Lorenzo Belluomini, Riccardo Nocini, Jessica Insolda, Ilaria Mariangela Scaglione, Jessica Menis, Michele Simbolo, Antonio Lugini, Federica Buzzacchino, Francesco Verderame, Francesca Spinnato, Giuseppe Aprile, Lorenzo Calvetti, Mario Occhi
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Enhanced tumor heterogeneity mediates poor prognosis in females with TP53 mutation in lung adenocarcinoma
Liudan Mai, Xinxin Yang, Chen Shao, Hongwei Yu, Fenqi Du, Jialu Liu, Yue Guan, Hao Li, Maopeng Yang, Hongxue Meng, Qiuju Zhang
International Journal of Biological Macromolecules.2025; 334: 149083. 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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Liquid biopsy in precision oncology: Current insights and future perspectives
Rajalakshmi Geetha, Subramania Iyer
Indian Journal of Precision Medicine and Molecular Medicine.2026; 2(1): 22. CrossRef
Metastatic Odyssey: Decoding the Genomic Journey from Primary Colorectal Cancer to Disseminated Disease
Taxiarchis Konstantinos Nikolouzakis, John Souglakos, Epameinondas Evangelos Kantidakis, Katerina Achilleos, Troye van Staden, Emmanuel Chrysos
Cancers.2026; 18(7): 1062. CrossRef
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
Evolution of Neo-RAS-WT in Circulating Tumor DNA from First-Line to Subsequent Therapies in Metastatic Colorectal Cancer
Marco Siringo, Michela De Meo, Irene Bottillo, Paola Grammatico, Enrico Cortesi, Chiara Nicolazzo, Paola Gazzaniga
Cancers.2025; 17(7): 1070. CrossRef
Liquid biopsy in gastrointestinal oncology: clinical applications and translational integration of ctDNA, CTCs, and sEVs
Rita Palieri, Maria De Luca, Francesco Balestra, Giorgia Panzetta, Claudio Lotesoriere, Federica Rizzi, Angela Dalia Ricci, Rita Mastrogiacomo, Maria Lucia Curri, Luigi Andrea Laghi, Gianluigi Giannelli, Nicoletta Depalo, Maria Principia Scavo
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Circulating Tumor DNA as a Biomarker for Precision Medicine in Prostate Cancer: A Systematic Review
Nouhaila Chanhih, Abdelilah Laraqui, Salma Hassine, Ahmed Ameur, Larbi Hamedoun, Hicham El Annaz, Rachid Abi, Mohamed Rida Tagajdid, Idriss Lahlou Amine, Khalid Ennibi, Abdelaziz Benjouad, Lamiae Belayachi
International Journal of Molecular Sciences.2025; 26(22): 11049. 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 resistance-driven cytokine alterations in the immunosuppressive microenvironment of colorectal cancer
Yingying Shao, Zewen Zhang, Yu Wang, Chunze Zhang, Erwei Liu, Haiyang Yu
Targetome.2026;[Epub] CrossRef
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.

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Survival benefit of adjuvant chemotherapy for perihilar cholangiocarcinoma: Impact of log odds of metastatic lymph node count
Jun Kawashima, Miho Akabane, Odysseas P. Chatzipanagiotou, Diamantis I. Tsilimigras, Zayed Rashid, Mujtaba Khalil, Abdullah Altaf, Yutaka Endo, Kota Sahara, Federico Aucejo, Hugo P. Marques, Beatriz Chumbinho, Tom Hugh, Shishir K. Maithel, Bas Groot Koerk
Surgery.2026; 191: 109913. CrossRef
Sex-based prognosis in industry-sponsored advanced solid tumor trials: an individual participant data meta-analysis of survival and adverse events
Rakchha Chhetri, Natansh D Modi, Bradley D Menz, Erik Cornelisse, David Postma, Nicole M Kuderer, Gary H Lyman, Sandra M Swain, Lee X Li, Ahmad Y Abuhelwa, Ross A McKinnon, Sina Vatandoust, Ganessan Kichenadasse, Andrew Rowland, Michael J Sorich, Ashley M
JNCI: Journal of the National Cancer Institute.2026;[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.2025; 49(3): 154. CrossRef
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; 49(3): T154. 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; 32(6): 4341. CrossRef
Neurobehavioral manifestations in female rats after intermittent exposure to an anticancer agent, paclitaxel
Deepika Pathak, K.P. Singh
Behavioural Pharmacology.2025; 36(5): 276. CrossRef
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Anna Carollo, Lavinia Piazza, Alessio Provenzani
Clinical and Translational Science.2025;[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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Multi-gene DNA methylation profiles of tumor suppressor genes for prognostic prediction in gastric cancer
Soo Kyung Nam, Juhyeong Park, Yoonjin Kwak, Chinbayar Batochir, Eun-Bi Kim, Seong-Ho Kong, Do Joong Park, Hyuk-Joon Lee, Han-Kwang Yang, Hye Seung Lee
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Bangxing Lin, Shizheng Tong, Chaokai Ba, Xiang Wang
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Ahmad Dawalibi, Mohamad Bakir, Khalid S. Mohammad
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TSPAN7 inhibits pancreatic cancer progression by suppressing DNA double-strand break repair and enhances sensitivity to immunochemotherapy
Hai Lin, Jiancong Zhou, Yaning Li, Lisi Luo, Yan Zeng, Xinyue Liang, Jiaping Yu, Chengying Ye, Pengfei Yang, Yujing Lin, Yufang Li, Linjuan Zeng
Biochemical Pharmacology.2025; 242: 117199. CrossRef
UBC9 overexpression promotes proliferation and metastasis in gastric cancer via ATF2
QingShui Wang, ShengZhao Li, YiNing Xu, Yuluo Chen, Chao Xu, QiuYan He, Yan Ye, YiMin Huang, Yue Wu, KeJia Guo, YaJuan Wei, Yide Huang, Yan Liu, Qing Lin, Shanshan Wang, Feng Li, Minghan Huang, FangQin Xue, Yao Lin
World Journal of Surgical Oncology.2025;[Epub] CrossRef
Migrasome-Related Prognostic Genes in Gastric Cancer: A Transcriptomic and Immunotherapeutic Analysis
Wei Qiu, Ke Zhang, Wei Hu, DongSheng Liu
OncoTargets and Therapy.2025; Volume 18: 873. CrossRef
Global and Sex-Stratified Genome-Wide Association Study of Long COVID Based on Patient-Driven Symptom Recall
Sara Polo-Alonso, Álvaro Hernáez, Irene Dégano, Ruth Martí-Lluch, Mel·lina Pinsach-Abuin, Roberto Elosua, Isaac Subirana, Marta Puigmulé, Alexandra Pérez, Raquel Cruz, Silvia Diz-de Almeida, Eulàlia Puigdecanet, Elisabet Selga, Xavier Nogues, Joan Masclan
International Journal of Molecular Sciences.2025; 26(18): 9252. CrossRef
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
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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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Predictive and Prognostic Value of p16 in Head and Neck Squamous Cell Carcinoma Patients Treated with Molecular Targeted Agents or Immune Checkpoint Inhibitors: Subgroup Analysis of the TRIUMPH Study
Hyerim Ha, Sang Hoon Chun, Yun-Gyoo Lee, Hyun Chang, Jang Ho Cho, Der Sheng Sun, Sang Hee Cho, Jung Hye Kwon, Kyoung Eun Lee, In Gyu Hwang, Hyo Jung Kim, Bhumsuk Keam, Seong Hoon Shin, Sung-Bae Kim, Joo Hang Kim, Hwan Jung Yun
Cancer Investigation.2026; 44(5): 479. CrossRef
GARD: Genomic Data-Based Drug Repurposing in Head and Neck Cancer with Large Language Model Validation
Pradham Tanikella, William Nenad, Christophe Courtine, Yifan Dai, Qingying Deng, Baiming Zou, Nosayaba Osazuwa-Peters, Travis P. Schrank, Di Wu
Cancers.2026; 18(5): 757. CrossRef
Expression and prognostic relevance of FGF19-KLB-FGFR4 pathway proteins and tumor microenvironment-related proteins in oral squamous cell carcinoma
Junichi Misumi, Kenichiro Uchida, Ryo Nonaka, Katsuaki Mishima
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology.2026;[Epub] CrossRef
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
Functional Characterization of Variants of Unknown Significance of Fibroblast Growth Factor Receptors 1-4 and Comparison With AI Model–Based Prediction
Martin Ziegler, Nadira Khoury, Louisa Maxine Hommerich, Heike Adler, Sonja Loges
JCO Precision Oncology.2025;[Epub] CrossRef
Prevalence and biological impact of clinically relevant gene fusions in head and neck cancers
Emily L. Hoskins, Raven Vella, Julie W. Reeser, Michele R. Wing, Eric Samorodnitsky, Altan Turkoglu, Leah Stein, Elizabeth Breuning, Zachary A. Risch, Wilnelly M. Hernandez-Sanchez, Lianbo Yu, Michelle Churchman, Nancy Single, Jad Chahoud, Antonio Jimeno,
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Molecular insights into immune evasion in head and neck squamous cell carcinomas: Toward a promising treatment strategy
HYEON JI KIM, BO KYUNG JOO, JIN-SEOK BYUN, DO-YEON KIM
Oncology Research.2025; 33(6): 1271. 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
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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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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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Ryuya Yamamoto, Yoko M. Nakao, Satomi Yoshida, Koji Kawakami
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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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Susanny J. Beltran, Lainey Dorris, Marie Hamel, Shanelle Harvey, Mustafa Ozkaynak, Kenan Sualp
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Catia Carconi, Gabriele Capurso, Martina Abati, Monica Maria Vincenzi, Alice Burini, Sara Cardellini, Maddalena Pavarini, Maria Giulia Ubeira-Gabellini, Diego Palumbo, Nicolò Pecorelli, Marina Macchini, Nicole Liscia, Antonino Campisi, Giovanni Guarneri,
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Clinicians’ Prediction of Survival Is Most Useful for Palliative Care Referral
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Palliative Medicine Reports.2024;[Epub] 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.

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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
Treatment patterns, outcomes, healthcare resource utilization, and costs associated with locally advanced squamous cell carcinoma of the head and neck in Japan
Kenichi Nibu, Makoto Tahara, Noriko Yoshimi, Ramzi Argoubi, Vanessa Rascon-Velasco, Makan Rahshenas, Sarah Bobiak, Ember Lu
Frontiers in Oncology.2025;[Epub] CrossRef
Neoadjuvant Chemotherapy for Oropharyngeal Cancer Treatment De-Escalation: From Historical Failures to Contemporary HPV-Driven Paradigms
Alvaro Sanabria, Juan P. Rodrigo, Anna Luíza Damaceno Araújo, Luiz P. Kowalski
Cancers.2025; 18(1): 23. 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
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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
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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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Hyperprogressive disease in carcinoma induced by immune checkpoint inhibitor therapy: a systematic review
JiaJu Xu, ChunXiao Ni, Lidong Qin, Ping Wang, JiaJu Xu
Clinical and Translational Oncology.2026;[Epub] CrossRef
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Angeline A. Truong, Savinnie Ho, Rex H. Lee, Xin Wu, Hyunseok Kang, Ivan H. El‐Sayed, Jonathan R. George, Chase M. Heaton, Ilya Likhterov, Mary Jue Xu, Patrick K. Ha, Alain P. Algazi, Katherine C. Wai
Head & Neck.2026;[Epub] CrossRef
Neutrophil‐to‐Lymphocyte Ratio and Pembrolizumab Outcomes in Oral Cavity Squamous Cell Carcinoma
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; 47(6): 1621. CrossRef
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Marianna Caterino, Giorgio Lo Giudice, Vincenzo Damiano, Francesco Perri, Guido Giordano, Davide Ciardiello, Aurora Mirabile, Mario Pirozzi, Andrea Pietro Sponghini, Vincenzo Ricci, Liliana Montella, Raffaele Addeo, Francesca Vignani, Vincenzo Famiglietti
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Prognostic factors and overall survival for recurrent and metastatic head and neck squamous cell carcinoma: a multicenter retrospective analysis
Kazufumi Obata, Satoshi Kano, Akira Ohkoshi, Akito Kakiuchi, Takahiro Inoue, Jun Taguchi, Ai Tagawa, Daisuke Matsushita, Jun Miyaguchi, Tentaro Endo, Ryo Ishii, Kazue Ito, Eiichi Ishida, Takahiro Suzuki, Naoto Araki, Tomotaka Kawase, Kenichi Takano
Japanese Journal of Clinical Oncology.2025; 55(9): 1013. CrossRef
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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
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Quan Wang, Xiangzhi Yin, Shengxia Wang, Haijun Lu
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Dong Hyun Kim, Seo Yoon Jang, Bhumsuk Keam
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Piero Giuseppe Meliante, Federica Zoccali, Marco de Vincentiis, Massimo Ralli, Carla Petrella, Marco Fiore, Antonio Minni, Christian Barbato
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Tibera K. Rugambwa, Omar Abdihamid, Xiangyang Zhang, Yinghui Peng, Changjing Cai, Hong Shen, Shan Zeng, Wei Qiu
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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
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Dengxiong Kang, Siping Liu, Xin Yuan, Shenxiang Liu, Zhengrong Zhang, Zhilian He, Xudong Yin, Haiyan Mao
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Jun-Liang Li, Tsai-Ling Hsieh, Ming-Che Ou, Frank Cheau-Feng Lin, Stella Chin-Shaw Tsai
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Yukinori Takenaka, Ryohei Oya, Norihiko Takemoto, Hidenori Inohara
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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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Yoonjin Kwak, Jeong Mo Bae, Hye Seung Lee
Cancer Research and Treatment.2026; 58(1): 1. CrossRef
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Anuj Kishor Patel, Nilay S. Sethi, Haeseong Park
JAMA.2026; 335(5): 439. CrossRef
Perioperative chemotherapy for gastric cancer patients with microsatellite instability or deficient mismatch repair: A systematic review and meta‐analysis
Baike Liu, Chaoyong Shen, Xiaonan Yin, Tianxiang Jiang, Yihui Han, Ruiwan Yuan, Yuan Yin, Zhaolun Cai, Bo Zhang
Cancer.2025;[Epub] CrossRef
Management of Microsatellite Instability High (MSI-H) Gastroesophageal Adenocarcinoma
Katherine I. Zhou, Brent A. Hanks, John H. Strickler
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The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023
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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
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Satya Das, Taymeyah Al-Toubah, Jonathan Strosberg
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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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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.

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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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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.

Citations

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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
Difficult Conversations and Painful Decisions: When Should Patients with Progressive Cancer Stop Chemotherapy?
Jeanine Staples, Varvara Mazina, Bethany-Rose Daubman, Annekathryn Goodman
Journal of Cancer Therapy.2022; 13(01): 20. 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
Best Practice & Research Clinical Gastroenterology.2021; 50-51: 101727. CrossRef
Influencing Factors and Effects of Treatment on Quality of Life in Patients With Gastric Cancer—A Systematic Review
Sophia Kristina Rupp, Andreas Stengel
Frontiers in Psychiatry.2021;[Epub] CrossRef
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
Annals of Surgical Treatment and Research.2020; 98(5): 262. CrossRef
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.

Citations

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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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Susan E. Jorge, Antonio R. Lucena-Araujo, Hiroyuki Yasuda, Zofia Piotrowska, Geoffrey R. Oxnard, Deepa Rangachari, Mark S. Huberman, Lecia V. Sequist, Susumu S. Kobayashi, Daniel B. Costa
Clinical Cancer Research.2018; 24(24): 6548. CrossRef

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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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MTHFR polymorphism is associated with increased adverse events and poor clinical outcomes in gastric cancer patients with adjuvant S-1 chemotherapy
Minsu Kang, Jin Won Kim, Ju Hyun Lee, Lyoung Hyo Kim, Woochan Park, So Hyun Kang, Young Suk Park, Ji-Won Kim, Hyeon Jeong Oh, Sang-Hoon Ahn, Yun-Suhk Suh, Do Joong Park, Hye Seung Lee, Hyung-Ho Kim, Keun-Wook Lee
Scientific Reports.2026;[Epub] CrossRef
Incidence and risk factors related to ocular adverse effects caused by S-1 chemotherapy
Tomoyuki Kamao, Masakazu Yamada, Atsushi Shiraishi, Jo Sakai, Yuichi Ohashi, Masashi Mimura, Yoshitsugu Inoue, Kazuyoshi Ohtomo, Tai-ichiro Chikama, Chika Miyazaki, Yuka Hosotani, Toshihito Furukawa
Japanese Journal of Ophthalmology.2026; 70(3): 527. CrossRef
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; 69(3): 447. CrossRef
Efficacy and Safety of a 3‐Weekly TS‐1 Adjuvant Regimen in Advanced Gastric Cancer: A Pilot Study
Jihong Bae, Joo‐Hwan Park, Young Saing Kim, Hee Kyung Ahn, Eun Kyung Cho, Dong Bok Shin, Ji‐Hyeon Park, Jun‐Young Yang, Woon Kee Lee, Sun Jin Sym
Cancer Medicine.2025;[Epub] CrossRef
Comparing Analyte Concentrations in Paired Tear Fluid and Blood Samples
Yutong Wang, Li Liang, Rudy M. M. A. Nuijts, Marlies Gijs
Current Eye Research.2025; : 1. 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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Relative Clinical Efficacy and Safety of Second- or Later-Line Treatments for Advanced and Metastatic Gastric Cancer: A Rapid Review and Network Meta-Analysis
Shikha Sharma, David McConnell, Niamh Carey, Jacintha O’Sullivan, Patrick Kearns, Maeve Lowery, Laura McCullagh, S Sharma, D McConnell, N Carey, J O’Sullivan, P Kearns, M Lowery, L McCullagh
Journal of Gastrointestinal Cancer.2026;[Epub] CrossRef
Network Meta-analysis of Randomized Controlled Trials in Patients with Previously Treated Advanced Gastric or Gastroesophageal Junction Cancer: Comparisons Involving Ramucirumab
Yulia D’yachkova, Astra M. Liepa, Rajat Goel, Veronika Earley-Valovic, Abby Paine, Palvi Gupta, Kaisa Taipale
Journal of Gastrointestinal Cancer.2025;[Epub] CrossRef
Mismatch between evidence and related clinical recommendations about the treatment of advanced esophageal cancer patients with anticancer drugs: A critical historical review
Xavier Bonfill Cosp, Olga Savall-Esteve, Javier Bracchiglione, Carolina Requeijo, Marilina Santero
Journal of Cancer Policy.2025; 44: 100580. 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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Shih Jia Janice Tan, Emile Kwong-Wei Tan, Yvonne Ying Ru Ng, Rehena Sultana, John Carson Allen, Isaac Seow-En, Ronnie Mathew, Aik Yong Chok
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