Cancer Research and Treatment

Original Articles

Association between Tumor Size at the Time of Disease Progression and Survival Outcomes: Chi Hoon Maeng, Bum Jun Kim, Myung-Ju Ahn, In Sil Choi, Dae Young Zang, Bo-Hyung Kim, Minji Kwon, Dae Seog Heo, Bhumsuk Keam; Received July 24, 2024 Accepted October 20, 2024 Published online October 22, 2024; DOI: https://doi.org/10.4143/crt.2024.690 [Accepted]

Abstract PDF: Purpose
This study evaluates the prognostic significance of tumor size at disease progression (PD) and depth of response (DOR) in cancer patients.
Materials and Methods
We performed post hoc analysis using data from six prospective clinical trials conducted by the Korean Cancer Study Group. Patients with tumor size at PD was categorized into ‘Mild PD’ and ‘Significant PD’ based on the cutoff values of relative change from baseline using maximally selected rank statistics. The overall survival (OS) and progression-free survival (PFS) were compared between PD and DOR categories.
Results
Among the 194 evaluable patients, 130 experienced PD. A 35.48% decrease from baseline in tumor size at PD was chosen for the cutoff between mild and significant PD for OS (mild PD: tumor size from the baseline ≤ −35.48%; significant PD > −35.48%). The mild PD had superior OS compared to the significant PD (25.8 vs. 12.8 months; Hazard ratio [HR] 0.47, 95% CI 0.266-0.843, p=0.009). When using an exploratory cutoff based on whether the tumor size was below vs. exceeded from the baseline (mild PD: tumor size from the baseline ≤ 0%; significant PD > 0%), OS remained significantly longer in the mild PD (17.1 vs. 11.8 months; HR 0.60, 95% CI 0.392-0.932, p=0.021). The greatest DOR was associated with the longest OS and PFS (p<0.001 for both).
Conclusion
Tumor size at PD and DOR were significant prognostic factors for progressive disease. Maintaining a sufficiently reduced tumor size even during PD was associated with better survival outcomes.

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Induction of Apoptosis in Intestinal Toxicity to a Histone Deacetylase Inhibitor in a Phase I Study with Pelvic Radiotherapy: Erta Kalanxhi, Karianne Risberg, Imon S. Barua, Svein Dueland, Stein Waagene, Solveig Norheim Andersen, Solveig J. Pettersen, Jessica M. Lindvall, Kathrine Røe Redalen, Kjersti Flatmark, Anne Hansen Ree; Cancer Res Treat. 2017;49(2):374-386. Published online July 28, 2016; DOI: https://doi.org/10.4143/crt.2016.080

Purpose
When integrating molecularly targeted compounds in radiotherapy, synergistic effects of the systemic agent and radiation may extend the limits of patient tolerance, increasing the demand for understanding the pathophysiological mechanisms of treatment toxicity. In this Pelvic Radiation and Vorinostat (PRAVO) study, we investigated mechanisms of adverse effects in response to the histone deacetylase (HDAC) inhibitor vorinostat (suberoylanilide hydroxamic acid, SAHA) when administered as a potential radiosensitiser.
Materials and Methods
This phase I study for advanced gastrointestinal carcinoma was conducted in sequential patient cohorts exposed to escalating doses of vorinostat combined with standard-fractionated palliative radiotherapy to pelvic target volumes. Gene expression microarray analysis of the study patient peripheral blood mononuclear cells (PBMC) was followed by functional validation in cultured cell lines and mice treated with SAHA.
Results
PBMC transcriptional responses to vorinostat, including induction of apoptosis, were confined to the patient cohort reporting dose-limiting intestinal toxicities. At relevant SAHA concentrations, apoptotic features (annexin V staining and caspase 3/7 activation, but not poly-(ADP-ribose)-polymerase cleavage) were observed in cultured intestinal epithelial cells. Moreover, SAHA-treated mice displayed significant weight loss.
Conclusion
The PRAVO study design implemented a strategy to explore treatment toxicity caused by an HDAC inhibitor when combined with radiotherapy and enabled the identification of apoptosis as a potential mechanism responsible for the dose-limiting effects of vorinostat. To the best of our knowledge, this is the first report deciphering mechanisms of normal tissue adverse effects in response to an HDAC inhibitor within a combined-modality treatment regimen.

Citations

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Effect of MicroRNA-210 on the Growth of Ovarian Cancer Cells and the Efficacy of Radiotherapy
Yinlong Zhao, Shirui Liu, Yu Wen, Lili Zhong
Gynecologic and Obstetric Investigation.2021; 86(1-2): 71. CrossRef
Valproic Acid Downregulates Cytokine Expression in Human Macrophages Infected with Dengue Virus
Félix G. Delgado, Paola Cárdenas, Jaime E. Castellanos
Diseases.2018; 6(3): 59. CrossRef
Synthesis, cytotoxic activity, and mode of action of new Santacruzamate A analogs
Silmara N. Andrade, Fernanda C. G. Evangelista, Diego Seckler, Deisielly R. Marques, Túlio R. Freitas, Renata R. Nunes, Júlia T. Oliveira, Rosy I. M. A. Ribeiro, Hélio B. Santos, Ralph G. Thomé, Alex G. Taranto, Fabio V. Santos, Gustavo H. R. Viana, Rossi
Medicinal Chemistry Research.2018; 27(11-12): 2397. CrossRef
Radiosensitization In Vivo by Histone Deacetylase Inhibition with No Increase in Early Normal Tissue Radiation Toxicity
Blaz Groselj, Jia-Ling Ruan, Helen Scott, Jessica Gorrill, Judith Nicholson, Jacqueline Kelly, Selvakumar Anbalagan, James Thompson, Michael R.L. Stratford, Sarah J. Jevons, Ester M. Hammond, Cheryl L. Scudamore, Martin Kerr, Anne E. Kiltie
Molecular Cancer Therapeutics.2018; 17(2): 381. CrossRef

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Analysis of Clinical Trials in the Journal of Korean Cancer Association for the Last Ten Years: Y S Park; J Korean Cancer Assoc. 2000;32(2):431-438.

Abstract PDF: PURPOSE
In Korea, many clinical trials have been published in medical journals. However, there has yet to be a study focusing on the scientific competence of the planning, execution and result interpretation of these reports. Therefore, this paper analyzed the clinical trials in the Journal of Korean Cancer Association for the last 10 years.
MATERIALS AND METHODS
All the clinical trials were analyzed according to the characteristics of clinical trial, disease, types and goals of treatment, The prospective studies were analyzed according to the competence of objectives, methods, results, and conclusion section. Clinical trials of surgical treatment were excluded from this study.
RESULTS
A total 223 (20.6%) out of 1,0S2 papers were reports of clinical trials. Of all the elinical trials, phase II, prospective, and single center studies were most common. Among 157 studies (70.4%) that were prospective, 29 studies (18.5%) did not clearly define eligibility criteria. The most common defect in the results was the lack of patients for the analysis (68 trials, 43.3%), and the median size of the trial was 30 patients. Statistical errors were found in 38 trials (24.3%).
CONCLUSION
A lot of clinical trials reported in the Journal of Korean Cancer Association need to be improved in tenns of quality. Also, the editors should review the submitted reports more thoroughly.

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