Cancer Research and Treatment

Original Articles

Effectiveness and Safety of Regorafenib and TAS-102 in Patients with Metastatic Colorectal Cancer: A Nationwide Population-Based Study in Taiwan: Ya-Wen Chang, Chun-Nan Kuo, Chia-Lun Chang, Jason C. Hsu, Yu Ko; Received April 16, 2024 Accepted November 16, 2024 Published online November 18, 2024; DOI: https://doi.org/10.4143/crt.2024.376 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study aimed to examine the real-world effectiveness and safety of regorafenib and trifluridine/tipiracil (TAS-102) in metastatic colorectal cancer (mCRC) patients in Taiwan.
Materials and Methods
Data were extracted from Taiwan’s National Health Insurance Research Database to evaluate the clinical outcomes of mCRC patients treated with either regorafenib or TAS-102 between 2016 and 2019. Overall survival (OS) was compared using Kaplan-Meier curves and Cox’s proportional hazard models, adjusting for age, sex, Quan-CCI score, liver metastases, number of metastatic sites, and the use of anti–epidermal growth factor receptor medications. Additionally, OS was compared between regorafenib monotherapy and TAS-102 monotherapy, excluding patients who had received both regorafenib and TAS-102.
Results
A total of 2,608 patients in the regorafenib group and 521 patients in the TAS-102 group were identified. The median OS was 6.5 months for regorafenib and 7.5 months for TAS-102, with a significant difference observed (p=0.001). The mean duration of treatment was similar for regorafenib and TAS-102 (108 days vs. 101 days) with no significant difference. The safety profiles of the two drugs were distinct; a higher proportion of patients in the regorafenib group had hypertension and hand-foot skin reaction while nausea and vomiting were more common in the TAS-102 group. In the subgroup analysis, patients receiving TAS-102 monotherapy showed significantly longer OS than those receiving regorafenib monotherapy.
Conclusion
The findings of this study indicated that TAS-102 had superior survival outcomes compared to regorafenib in mCRC patients. This study provides insights into the effectiveness and safety profiles of regorafenib and TAS-102 in Taiwan.

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Genitourinary cancer

Physical Activity and Bladder Cancer Risk: Findings of the Japan Collaborative Cohort Study: Hang An, Keyang Liu, Kokoro Shirai, Ryo Kawasaki, Akiko Tamakoshi, Hiroyasu Iso; Cancer Res Treat. 2024;56(2):616-623. Published online October 6, 2023; DOI: https://doi.org/10.4143/crt.2023.962

Abstract PDF Supplementary Material PubReader ePub

Purpose
The association of physical activity with the risk of bladder cancer remains inconsistent among Asian populations. We aimed to examine the association in a large Japanese cohort.
Materials and Methods
In a population-based prospective cohort study, a total of 50,374 Japanese adults aged 40-79 years without a history of cancer or cardiovascular disease who had information on physical activity from self-administrated questionnaires were used for analysis. We performed Cox proportional hazard models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident bladder cancer after adjusting for several potential confounders.
Results
During the median 17.5 years of follow-up, 153 incident bladder cancers (116 men and 37 women) were identified. After the multivariable adjustment, HRs (95% CI) of bladder cancer concerning those with recreational sports participation of 1-2 hr/wk, 3-4 hr/wk, and 5 hr/wk and more were 0.67 (0.38-1.20), 0.79 (0.36-1.74), and 0.28 (0.09-0.89), respectively (p for trend=0.017). Compared with mostly sitting at the workplace, occupational physical activity of standing and walking were associated with a lower risk of bladder cancer (HR, 0.53 [95% CI, 0.32 to 0.85]). Hours of daily walking were not associated with the risk. The lower risk of bladder cancer was more evident for recreational sports (HR, 0.33 [95% CI, 0.10 to 1.00]), and for occupational standing and walking activity at work (HR, 0.57 [95% CI, 0.33 to 0.98]) among men.
Conclusion
Recreational sports participation and occupational physical activity were inversely associated with the risk of bladder cancer among Japanese, especially in men.

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Physical Activity and Cancer Incidence and Mortality: Current Evidence and Biological Mechanisms
Joanna Kruk, Basil Hassan Aboul-Enein, Marta Ewelina Gołębiewska, Ewa Duchnik, Urszula Czerniak, Mariola Marchlewicz
Cancers.2025; 17(9): 1410. CrossRef

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Gastrointestinal cancer

Association between Metabolically Healthy Status and Risk of Gastrointestinal Cancer: Haozhe Cui, Fei Tian, Yongliang Chen, Xiangming Ma; Cancer Res Treat. 2024;56(1):238-246. Published online August 2, 2023; DOI: https://doi.org/10.4143/crt.2023.539

Abstract PDF Supplementary Material PubReader ePub

Purpose
Although obesity is associated with numerous diseases, the risks of disease may depend on metabolically healthy status. Nevertheless, it is unclear to whether metabolically healthy status affects risk of gastrointestinal (GI) cancer in general Chinese population.
Materials and Methods
A total of 114,995 participants who met the criteria were included from the Kailuan Study. The study participants were divided into four groups according to body mass index (BMI)/waist circumference (WC) and metabolic status. Incident of GI cancer (esophageal cancer, gastric cancer, liver cancer, biliary cancer, pancreatic cancer, and colorectal cancer) during 2006-2020 were confirmed by review of medical records. The Cox proportional hazard regression models were used to assess the association metabolically healthy status with the risk of GI cancer by calculating the hazard ratios (HR) and 95% confidence interval (CI).
Results
During a mean 13.76 years of follow-up, we documented 2,311 GI cancers. Multivariate Cox regression analysis showed that compared with the metabolically healthy normal-weight group, metabolically healthy obese (MHO) participants demonstrated an increased risk of developing GI cancer (HR, 1.54; 95% CI, 1.11 to 2.13) by BMI categories. However, such associations were not found for WC category. These associations were moderated by age, sex, and anatomical site of the tumor. Individuals with metabolic unhealthy normal-weight or metabolic unhealthy obesity phenotype also have an increased risk of GI cancer.
Conclusion
MHO phenotype was associated with increased risk of GI cancer. Moreover, individuals who complicated by metabolic unhealthy status have an increased risk of developing GI cancer. Hence, clinicians should consider the risk of incident GI cancer in people with abnormal metabolically healthy status and counsel them about metabolic fitness and weight control.

Citations

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Metabolic Phenotype and Risk of Obesity-Related Cancers in the Women’s Health Initiative
Prasoona Karra, Sheetal Hardikar, Maci Winn, Garnet L. Anderson, Benjamin Haaland, Aladdin H. Shadyab, Marian L. Neuhouser, Rebecca A. Seguin-Fowler, Cynthia A. Thomson, Mace Coday, Jean Wactawski-Wende, Marcia L. Stefanick, Xiaochen Zhang, Ting-Yuan Davi
Cancer Prevention Research.2025; 18(2): 63. CrossRef
Associations of Social Vulnerability and Race‐Ethnicity With Gastrointestinal Cancers in the United States
David J. Fei‐Zhang, David J. Bentrem, Jeffrey D. Wayne, Lifang Hou, Peiwen Fei, Timothy M. Pawlik
Cancer Medicine.2025;[Epub] CrossRef
Association between metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction subtypes and risk of colorectal cancer: A prospective cohort study
Yuan Li, Xiang-ming Ma, Jian-guo Jia, Li-ying Cao
Clinics and Research in Hepatology and Gastroenterology.2025; 49(5): 102573. CrossRef
Association between transitions in metabolic health and colorectal cancer across categories of body size phenotype: a prospective cohort study
Qian Liu, Fei Si, Yuntao Wu, Jing Yu
Obesity.2024; 32(10): 1948. CrossRef
Gastric Cancer - Epidemiology, Modifiable and Non-modifiable Risk Factors, Challenges and Opportunities: An Updated Review
Tajul Islam Mamun, Sabrina Younus, Md. Hashibur Rahman
Cancer Treatment and Research Communications.2024; : 100845. CrossRef
Research Progress of Scutellaria baicalensis in the Treatment of Gastrointestinal Cancer
Lankang Wang, Baoyi Ni, Jia Wang, Jilai Zhou, Junyi Wang, Jiakang Jiang, Yutong Sui, Yaoyao Tian, Feng Gao, Yufeng Lyu
Integrative Cancer Therapies.2024;[Epub] CrossRef

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Gastrointestinal Cancer

Fasting Blood Glucose, Cholesterol, and Risk of Primary Liver Cancer: The Kailuan Study: Xiangming Ma, Haozhe Cui, Miaomiao Sun, Qian Liu, Xining Liu, Guangjian Li, Yaochen Wei, Qingjiang Fu, Siqing Liu, Liying Cao; Cancer Res Treat. 2021;53(4):1113-1122. Published online January 19, 2021; DOI: https://doi.org/10.4143/crt.2020.817

Abstract PDF PubReader ePub

Purpose
The influence of fasting blood glucose (FBG) and cholesterolemia primary liver cancer (PLC) in china was analyzed via a large prospective cohort study based on a community population, and the combined effects between them were investigated.
Materials and Methods
Overall, 98,936 staff from the Kailuan Group who participated in and finished physical examinations between 2006 and 2007 were included in the cohort study. Their medical information was collected and they were followed up after examination. The correlations of serum FBG or TC with PLC were analyzed. Then, we categorized all staff into four groups: normal FBG/ non-hypocholesterolemia, normal FBG/hypocholesterolemia, elevated FBG/non-hypocholesterolemia, elevated FBG/hypocholesterolemia and normal FBG/ non-hypocholesterolemia was used as a control group. The combined effects of elevated FBG and hypocholesterolemia with PLC were analyzed using the Age-scale Cox proportional hazard regression model.
Results
During 1,134,843.68 person*years follow up, a total of 388 PLC cases occured. We found the elevated FBG and hypocholesterolemia increases the risk for PLC, respectively. Compared with the non-hypocholesterolemia/normal FBG group, the risk of PLC was significantly increased in the non-hypocholesterolemia/elevated FBG group (HR=1.19,95%CI 0.88–1.62) and hypocholesterolemia/normal FBG group (HR=1.53,95%CI 1.19–1.97), and in the hypocholesterolemia/elevated FBG group (HR=3.16 95%CI2.13-4.69). And, a significant interaction effect was found of FBG and TC on PLC. All results were independent from the influence of liver disease.
Conclusion
Elevated serum FBG and hypocholesterolemia are risk factors for PLC, especially when combined. Thus, for the prevention and treatment of PLC, serum FBG and TC levels should be investigated.

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Prognostic value of AFP-L3 and Des-γ-carboxy prothrombin in advanced primary liver cancer treated with Sorafenib and transarterial chemoembolization
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Dongna Zhao, Haozhe Cui, Zhiqiang Shao, Liying Cao
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Lizhen Zhang, Zhongge Wang, Ruirui Chen, Zhiyuan Cheng, Jingli Yang, Jing Li, Siyu Li, Yarong Chen, Lulu Xu, Yujia Hu, Yana Bai
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Association between Body Mass Index and Gastric Cancer Risk According to Effect Modification by Helicobacter pylori Infection: Jieun Jang, Eun-Jung Cho, Yunji Hwang, Elisabete Weiderpass, Choonghyun Ahn, Jeoungbin Choi, Soung-Hoon Chang, Hai-Rim Shin, Min Kyung Lim, Keun-Young Yoo, Sue K. Park; Cancer Res Treat. 2019;51(3):1107-1116. Published online November 21, 2018; DOI: https://doi.org/10.4143/crt.2018.182

Abstract PDF Supplementary Material PubReader ePub

Purpose
Few studies investigated roles of body mass index (BMI) on gastric cancer (GC) risk according to Helicobacter pylori infection status. This study was conducted to evaluate associations between BMI and GC risk with consideration of H. pylori infection information.
Materials and Methods
We performed a case-cohort study (n=2,458) that consists of a subcohort, (n=2,193 including 67 GC incident cases) randomly selected from the Korean Multicenter Cancer Cohort (KMCC) and 265 incident GC cases outside of the subcohort. H. pylori infection was assessed using an immunoblot assay. GC risk according to BMI was evaluated by calculating hazard ratios (HRs) and their 95% confidence intervals (95% CIs) using weighted Cox hazard regression model.
Results
Increased GC risk in lower BMI group (< 23 kg/m²) with marginal significance, (HR, 1.32; 95% CI, 0.98 to 1.77) compared to the reference group (BMI of 23-24.9 kg/m²) was observed. In the H. pylori non-infection, both lower (< 23 kg/m²) and higher BMI (≥ 25 kg/m²) showed non-significantly increased GC risk (HR, 10.82; 95% CI, 1.25 to 93.60 and HR, 11.33; 95% CI, 1.13 to 113.66, respectively). However, these U-shaped associations between BMI and GC risk were not observed in the group who had ever been infected by H. pylori.
Conclusion
This study suggests the U-shaped associations between BMI and GC risk, especially in subjects who had never been infected by H. pylori.

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Ethnic-specific associations between body mass index and gastric cancer: a Mendelian randomization study in European and Korean populations
Sangjun Lee, Sue K. Park
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Sangjun Lee, Han-Kwang Yang, Hyuk-Joon Lee, Do Joong Park, Seong-Ho Kong, Sue K. Park
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Association between metabolic syndrome and gastric cancer risk: results from the Health Examinees Study
Dan Huang, Woo-Kyoung Shin, Katherine De la Torre, Hwi-Won Lee, Sukhong Min, Aesun Shin, Jong-Koo Lee, Daehee Kang
Gastric Cancer.2023; 26(4): 481. CrossRef
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Priya Alagesan, Jessica C. Goodwin, Katherine S. Garman, Meira Epplein
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Obesity at early adulthood increases risk of gastric cancer from the Health Examinees-Gem (HEXA-G) study
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PLOS ONE.2022; 17(2): e0260826. CrossRef
Association between Body Mass Index and Risk of Gastric Cancer by Anatomic and Histologic Subtypes in Over 500,000 East and Southeast Asian Cohort Participants
Jieun Jang, Sangjun Lee, Kwang-Pil Ko, Sarah K. Abe, Md. Shafiur Rahman, Eiko Saito, Md. Rashedul Islam, Norie Sawada, Xiao-Ou Shu, Woon-Puay Koh, Atsuko Sadakane, Ichiro Tsuji, Jeongseon Kim, Isao Oze, Chisato Nagata, Shoichiro Tsugane, Hui Cai, Jian-Min
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Effectiveness of Gastric Cancer Screening on Gastric Cancer Incidence and Mortality in a Community-Based Prospective Cohort: Heewon Kim, Yunji Hwang, Hokyung Sung, Jieun Jang, Choonghyun Ahn, Sang Gyun Kim, Keun-Young Yoo, Sue K. Park; Cancer Res Treat. 2018;50(2):582-589. Published online June 9, 2017; DOI: https://doi.org/10.4143/crt.2017.048

Abstract PDF Supplementary Material PubReader ePub

Purpose
This study was performed to investigate the effectiveness of gastric cancer (GC) screening methods in a community-based prospective cohort of the Korean Multi-center Cancer Cohort (KMCC) with over a 10-year follow-up.
Materials and Methods
A total 10,909 and 4,773 subjects from the KMCC with information on gastroendoscopy (GE) and upper gastrointestinal series (UGIS) were included in this study. Cox proportional hazard model adjusted for age, sex, Helicobacter pylori infection, cigarette smoking, and alcohol drinking was used to estimate the hazard ratios (HRs) and 95% confidence interval (CI).
Results
The GE screened subjects had almost half the risk of GC-specific death than that of unscreened subjects (HR, 0.58; 95% CI, 0.36 to 0.94). Among the GC patients, GE screenees had a 2.24-fold higher survival rate than that of the non-screenees (95% CI, 1.61 to 3.11). In particular, GE screenees who underwent two or more screening episodes had a higher survival rate than that of the non-screenees (HR, 13.11; 95% CI, 7.38 to 23.30). The effectiveness of GE screening on reduced GC mortality and increased survival rate of GC patients was better in elderly subjects (≥ 65 years old) (HR, 0.47; 95% CI, 0.24 to 0.95 and HR, 8.84; 95% CI, 3.63 to 21.57, respectively) than that in younger subjects (< 65 years old) (HR, 0.66; 95% CI, 0.34 to 1.29 and HR, 1.83; 95% CI, 1.24 to 2.68, respectively). In contrast, UGIS screening had no significant relation to GC mortality and survival.
Conclusion
The findings of this study suggest that a decreased GC-specific mortality and improved survival rate in GC patients can be achieved through GE screening.

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Light Alcohol Drinking and Risk of Cancer: A Meta-Analysis of Cohort Studies: Yoon-Jung Choi, Seung-Kwon Myung, Ji-Ho Lee; Cancer Res Treat. 2018;50(2):474-487. Published online May 22, 2017; DOI: https://doi.org/10.4143/crt.2017.094

Abstract PDF Supplementary Material PubReader ePub

Purpose
The purpose of this study was to determine whether light alcohol drinking increases the risk of cancer by using a meta-analysis of cohort studies because the newly revised 2015 European Code against Cancer fourth edition on alcohol and cancer was based on critical flaws in the interpretation and citation of the previous meta-analyses.
Materials and Methods
PubMed and EMBASE were searched in April, 2016. Two authors independently reviewed and selected cohort studies on the association between very light (≤ 0.5 drink/day), light (≤ 1 drink/day), or moderate drinking (1-2 drinks/day) and the risk of cancer incidence and mortality. A pooled relative riskwith its 95% confidence intervalwas calculated by a randomeffects meta-analysis. Main outcome measures were cancer incidence and mortality.
Results
A total of 60 cohort studies from 135 articles were included in the final analysis. Very light drinking or light drinking was not associated with the incidence of most cancers except for female breast cancer in women and male colorectal cancer. Conversely, light drinking was associated with a decreased incidence of both female and male lung cancer significantly and both female and male thyroid cancer marginally significantly. Moderate drinking significantly increased the incidence of male colorectal cancer and female breast cancer,whereas it decreased the incidence of both female and male hematologic malignancy.
Conclusion
We found that very light or light alcohol drinking was not associated with the risk of most of the common cancers except for the mild increase in the incidence of breast cancer in women and colorectal cancer in men.

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The Clinical Significance of Occult Gastrointestinal Primary Tumours in Metastatic Cancer: A Population Retrospective Cohort Study: Malek B. Hannouf, Eric Winquist, Salaheddin M. Mahmud, Muriel Brackstone, Sisira Sarma, George Rodrigues, Peter K. Rogan, Jeffrey S. Hoch, Gregory S. Zaric; Cancer Res Treat. 2018;50(1):183-194. Published online March 21, 2017; DOI: https://doi.org/10.4143/crt.2016.532

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to estimate the incidence of occult gastrointestinal (GI) primary tumours in patients with metastatic cancer of uncertain primary origin and evaluate their influence on treatments and overall survival (OS).
Materials and Methods
We used population heath data from Manitoba, Canada to identify all patients initially diagnosed with metastatic cancer between 2002 and 2011. We defined patients to have “occult” primary tumour if the primary was found at least 6 months after initial diagnosis. Otherwise, we considered primary tumours as “obvious.” We used propensity-score methods to match each patient with occult GI tumour to four patients with obvious GI tumour on all known clinicopathologic features. We compared treatments and 2-year survival data between the two patient groups and assessed treatment effect on OS using Cox regression adjustment.
Results
Eighty-three patients had occult GI primary tumours, accounting for 17.6% of men and 14% of women with metastatic cancer of uncertain primary. A 1:4 matching created a matched group of 332 patients with obvious GI primary tumour. Occult cases compared to the matched group were less likely to receive surgical interventions and targeted biological therapy, and more likely to receive cytotoxic empiric chemotherapeutic agents. Having an occult GI tumour was associated with reduced OS and appeared to be a nonsignificant independent predictor of OS when adjusting for treatment differences.
Conclusion
GI tumours are the most common occult primary tumours in men and the second most common in women. Patients with occult GI primary tumours are potentially being undertreated with available GI site-specific and targeted therapies.

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Relationship between metastasis and second primary cancers in women with breast cancer
Chaofan Li, Mengjie Liu, Jia Li, Xixi Zhao, Yusheng Wang, Xi Chen, Weiwei Wang, Shiyu Sun, Cong Feng, Yifan Cai, Fei Wu, Chong Du, Yinbin Zhang, Shuqun Zhang, Jingkun Qu
Frontiers in Oncology.2022;[Epub] CrossRef
The Potential Clinical and Economic Value of Primary Tumour Identification in Metastatic Cancer of Unknown Primary Tumour: A Population-Based Retrospective Matched Cohort Study
Malek B. Hannouf, Eric Winquist, Salaheddin M. Mahmud, Muriel Brackstone, Sisira Sarma, George Rodrigues, Peter K. Rogan, Jeffrey S. Hoch, Gregory S. Zaric
PharmacoEconomics - Open.2018; 2(3): 255. CrossRef

9,496 View
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Meta-Analysis

Alcohol Intake and Risk of Thyroid Cancer: A Meta-Analysis of Observational Studies: Seung-Hee Hong, Seung-Kwon Myung, Hyeon Suk Kim, The Korean Meta-Analysis (KORMA) Study Group; Cancer Res Treat. 2017;49(2):534-547. Published online July 7, 2016; DOI: https://doi.org/10.4143/crt.2016.161

Abstract PDF PubReader ePub

Purpose
The purpose of this study was to assess whether alcohol intake is associated with the risk of thyroid cancer by a meta-analysis of observational studies.
Materials and Methods
We searched PubMed and EMBASE in June of 2015 to locate eligible studies. We included observational studies such as cross-sectional studies, case-control studies, and cohort studies reporting odd ratios (ORs) or relative risk (RRs) with 95% confidence intervals (CIs).
Results
We included 33 observational studies with two cross-sectional studies, 20 case-controls studies, and 11 cohort studies, which involved a total of 7,725 thyroid cancer patients and 3,113,679 participants without thyroid cancer in the final analysis. In the fixed-effect model meta-analysis of all 33 studies, we found that alcohol intake was consistently associated with a decreased risk of thyroid cancer (OR or RR, 0.74; 95% CI, 0.67 to 0.83; I2=38.6%). In the subgroup meta-analysis by type of study, alcohol intake also decreased the risk of thyroid cancer in both case-control studies (OR, 0.77; 95% CI, 0.65 to 0.92; I2=29.5%; n=20) and cohort studies (RR, 0.70; 95% CI, 0.60 to 0.82; I2=0%; n=11). Moreover, subgroup meta-analyses by type of thyroid cancer, gender, amount of alcohol consumed, and methodological quality of study showed that alcohol intake was significantly associated with a decreased risk of thyroid cancer.
Conclusion
The current meta-analysis of observational studies found that, unlike most of other types of cancer, alcohol intake decreased the risk of thyroid cancer.

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