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Association between markers of glucose metabolism and risk of colorectal adenoma

Rampal S, Yang MH, Sung J, Son HJ, Choi YH, Lee JH, et al.

Gastroenterology, 2014 Jul;147(1):78-87.e3.
PMID: 24632359 DOI: 10.1053/j.gastro.2014.03.006

BACKGROUND & AIMS: Diabetes is a risk factor for colorectal cancer. We studied the association between markers of glucose metabolism and metabolic syndrome and the presence of colorectal adenomas in a large number of asymptomatic men and women attending a health screening program in South Korea. We also investigated whether these associations depend on adenoma location.
METHODS: In a cross-sectional study, we measured fasting levels of glucose, insulin, hemoglobin A1c, and C-peptide and calculated homeostatic model assessment (HOMA) values (used to quantify insulin resistance) for 19,361 asymptomatic South Korean subjects who underwent colonoscopy examinations from January 2006 to June 2009. Participants completed a standardized self-administered health questionnaire and a validated semiquantitative food frequency questionnaire. Blood samples were collected on the day of the colonoscopy; fasting blood samples were also collected. Robust Poisson regression was used to model the associations of glucose markers with the prevalence of any adenoma.
RESULTS: Using detailed multivariable-adjusted dose-response models, the prevalence ratios (aPR, 95% confidence interval [CI]) for any adenoma, comparing the 90th with the 10th percentile, were 1.08 (1.00-1.16; P = .04) for fasting glucose, 1.07 (0.99-1.15; P = .10) for insulin, 1.09 (1.02-1.18, P = .02) for HOMA, 1.09 (1.01-1.17; P = .02) for hemoglobin A1c, and 1.14 (1.05-1.24; P = .002) for C-peptide. The corresponding ratios for nonadvanced adenomas were 1.11 (0.99-1.25; P = .08), 1.10 (0.98-1.24; P = .12), 1.15 (1.02-1.29; P = .02), 1.14 (1.01-1.28; P = .03), and 1.20 (1.05-1.37; P = .007), respectively. The corresponding ratios for advanced adenomas were 1.32 (0.94-1.84; P = .11), 1.23 (0.87-1.75; P = .24), 1.30 (0.92-1.85; P = .14), 1.13 (0.79-1.61; P = .50), and 1.67 (1.15-2.42; P = .007), respectively. Metabolic syndrome was associated with the prevalence of any adenoma (aPR, 1.18; 95% CI, 1.13-1.24; P < .001), nonadvanced adenoma (aPR, 1.30; 95% CI, 1.20-1.40; P < .001), and advanced adenoma (aPR, 1.42; 95% CI, 1.14-1.78; P = .002). Associations were similar for adenomas located in the distal versus proximal colon.
CONCLUSIONS: Increasing levels of glucose, HOMA values, levels of hemoglobin A1c and C-peptide, and metabolic syndrome are significantly associated with the prevalence of adenomas. Adenomas should be added to the list of consequences of altered glucose metabolism.
Fulltext The prevalence of colorectal adenomas in asymptomatic Korean men and women

Yang MH, Rampal S, Sung J, Choi YH, Son HJ, Lee JH, et al.

Cancer Epidemiol Biomarkers Prev, 2014 Mar;23(3):499-507.
PMID: 24443404 DOI: 10.1158/1055-9965.EPI-13-0682

Colorectal cancer incidence is rapidly rising in many Asian countries, with rates approaching those of Western countries. This study aimed to evaluate the prevalence and trends of colorectal adenomas by age, sex, and risk strata in asymptomatic Koreans.
Fulltext Pan-Asian adaptation of the EHNS-ESMO-ESTRO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with squamous cell carcinoma of the head and neck

Keam B, Machiels JP, Kim HR, Licitra L, Golusinski W, Gregoire V, et al.

ESMO Open, 2021 Dec;6(6):100309.
PMID: 34844180 DOI: 10.1016/j.esmoop.2021.100309

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of squamous cell carcinoma (SCC) of the oral cavity, larynx, oropharynx and hypopharynx was published in 2020. It was therefore decided by both the ESMO and the Korean Society of Medical Oncology (KSMO) to convene a special, virtual guidelines meeting in July 2021 to adapt the ESMO 2020 guidelines to consider the potential ethnic differences associated with the treatment of SCCs of the head and neck (SCCHN) in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with SCCHN (excluding nasopharyngeal carcinomas) representing the oncological societies of Korea (KSMO), China (CSCO), India (ISMPO), Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of the current treatment practices and drug access restrictions in the different Asian countries. The latter was discussed when appropriate. This manuscript provides a series of expert recommendations (Clinical Practice Guidelines) which can be used to provide guidance to health care providers and clinicians for the optimisation of the diagnosis, treatment and management of patients with SCC of the oral cavity, larynx, oropharynx and hypopharynx across Asia.
Fulltext Gemcitabine, carboplatin, and Epstein-Barr virus-specific autologous cytotoxic T lymphocytes for recurrent or metastatic nasopharyngeal carcinoma: VANCE, an international randomized phase III trial

Toh HC, Yang MH, Wang HM, Hsieh CY, Chitapanarux I, Ho KF, et al.

Ann Oncol, 2024 Dec;35(12):1181-1190.
PMID: 39241963 DOI: 10.1016/j.annonc.2024.08.2344

BACKGROUND: Epstein-Barr virus-specific cytotoxic T lymphocyte (EBV-CTL) is an autologous adoptive T-cell immunotherapy generated from the blood of individuals and manufactured without genetic modification. In a previous phase II trial of locally recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) patients, first-line gemcitabine and carboplatin (GC) and EBV-CTL combination demonstrated objective antitumor EBV-CTL activity and a favorable safety profile. The present study explored whether this combined first-line chemo-immunotherapy strategy would produce superior clinical efficacy and better quality of life compared with conventional chemotherapy treatment.
PATIENTS AND METHODS: This multicenter, randomized, phase III trial evaluated the efficacy and safety of GC followed by EBV-CTL versus GC alone as first-line treatment of R/M NPC patients. Thirty clinical sites in Singapore, Malaysia, Taiwan, Thailand, and the USA were included. Subjects were randomized to first-line GC (four cycles) and EBV-CTL (six cycles) or GC (six cycles) in a 1 : 1 ratio. The primary outcome was overall survival (OS) and secondary outcomes included progression-free survival, objective response rate, clinical benefit rate, quality of life, and safety.
CLINICALTRIALS: gov identifier: NCT02578641.
RESULTS: A total of 330 subjects with NPC were enrolled. Most subjects in both treatment arms received four or more cycles of chemotherapy and most subjects in the GC + EBV-CTL group received two or more infusions of EBV-CTL. The central Good Manufacturing Practices (GMP) facility produced sufficient EBV-CTL for 94% of GC + EBV-CTL subjects. The median OS was 25.0 months in the GC + EBV-CTL group and 24.9 months in the GC group (hazard ratio = 1.19; 95% confidence interval 0.91-1.56; P = 0.194). Only one subject experienced a grade 2 serious adverse event related to EBV-CTL.
CONCLUSIONS: GC + EBV-CTL in subjects with R/M NPC demonstrated a favorable safety profile but no overall improvement in OS versus chemotherapy. This is the largest adoptive T-cell therapy trial reported in solid tumors to date.