Purpose: Radiotherapy (RT) remains a cornerstone of curative treatment for localized and locally advanced prostate cancer. However, dose escalation to improve tumor control is often constrained by the proximity of the rectum, which increases the risk of gastrointestinal (GI) and genitourinary toxicities. Biodegradable rectal spacers inserted between the prostate and rectum have emerged as an effective approach to reduce rectal radiation exposure. This guideline provides evidence-based recommendations on indications, contraindications, procedural standards, and clinical management for biodegradable rectal spacer insertion during prostate cancer RT. Materials and Methods: This guideline was developed by a multidisciplinary expert panel through a systematic review of the literature, analysis of international guidelines (National Comprehensive Cancer Network, European Association of Urology, American Society for Radiation Oncology), and expert consensus among radiation oncologists, radiologists, and urologists with clinical experience in spacer insertion. The strength of each recommendation and the level of evidence were classified according to the modified GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system. Results: Spacer insertion is conditionally recommended (Grade C, Level I) for patients receiving definitive external-beam RT without rectal invasion. It reduces the high-dose rectal irradiation volume (V70–75) by >50%, decreases acute GI toxicity, and helps maintain bowel-related quality of life. However, the benefit for late severe toxicity (grade 2 or higher) remains debated in recent meta-analyses. Contraindications include rectal invasion, anatomical inaccessibility, infection, and material hypersensitivity. Procedures should be performed under local anesthesia in a sterile environment by trained physicians. Short-course antibiotics and simulator-based training, including completion of multiple supervised cases, are advised. Conclusion Biodegradable rectal spacer insertion is clinically validated and effective in reducing acute rectal toxicity. Although pivotal trials demonstrated a favorable procedural safety profile, real-world postmarket data include reports of rare but severe procedural complications. This guideline provides standardized recommendations tailored to Korean clinical practice while remaining consistent with international standards, emphasizing the importance of operator training and careful patient selection.

γ-Radiation resistance is a major obstacle to the success of radiotherapy in colorectal cancer. Antioxidant-related factors contribute to resistance to radiation therapy and, therefore, are targets for improving the therapeutic response. In this study, we evaluated the molecular mechanisms underlying γ-radiation resistance using the colorectal cancer cell line SNUC5 and γ-radiation-resistant variant SNUC5/RR, including analyses of the role of nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor that regulates antioxidant enzymes, and related epigenetic regulators. Reactive oxygen species (ROS) levels, antioxidant enzyme expression, NRF2 expression, and nuclear translocation were higher in SNUC5/RR cells irradiated with or without 8 Gy than in SNUC5 cells. The DNA demethylase ten-eleven translocation 1 (TET1) expression and TET1 binding to the NRF2 promoter in SNUC5/RR cells were stronger than those in SNUC5 cells, indicating lower methylation of CpG islands in the NRF2 promoter.TET1 knockdown in SNUC5/RR cells suppressed NRF2 expression significantly. Additionally, histone mixed-lineage leukemia (MLL), a histone methyltransferase, was upregulated, leading to increased trimethylation of histone H3 lysine 4, whereas enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, was downregulated, leading to decreased trimethylation of histone H3 lysine 27. Histone deacetylase (HDAC) and histone acetyltransferase (HAT) levels were lower and higher in SNUC5/RR cells than in SNUC5 cells, respectively. MLL and HAT knockdown in SNUC5/RR cells irradiated with or without 8 Gy decreased levels of NRF2 and heme-oxygenase 1, resulting in enhanced γ-radiation sensitivity. These findings support NRF2 as a target for improving the response to radiotherapy in patients with colorectal cancer.

Purpose: The Korean Cancer Study Group (KCSG) is a nationwide cancer clinical trial group dedicated to advancing investigator-initiated trials (IITs) by conducting and supporting clinical trials. This study aims to review IITs conducted by KCSG and quantitatively evaluate the survival and financial benefits of IITs for patients. Materials and Methods: We reviewed IITs conducted by KCSG from 1998 to 2023, analyzing progression-free survival (PFS) and overall survival (OS) gains for participants. PFS and OS benefits were calculated as the difference in median survival times between the intervention and control groups, multiplied by the number of patients in the intervention group. Financial benefits were assessed based on the cost of investigational products provided. Results: From 1998 to 2023, KCSG conducted 310 IITs, with 133 completed and published. Of these, 21 were included in the survival analysis. The analysis revealed that 1,951 patients in the intervention groups gained a total of 2,558.4 months (213.2 years) of PFS and 2,501.6 months (208.5 years) of OS, with median gains of 1.31 months in PFS and 1.58 months in OS per patient. When analyzing only statistically significant results, PFS and OS gain per patients was 1.69 months and 3.02 months, respectively. Investigational drug cost analysis from six available IITs indicated that investigational products provided to 252 patients were valued at 10,400,077,294 won (approximately 8,046,481 US dollars), averaging about 41,270,148 won (approximately 31,930 US dollars) per patient. Conclusion Our findings, based on analysis of published research, suggest that IITs conducted by KCSG led to survival benefits for participants and, in some studies, may have provided financial benefits by providing investment drugs.

Background/Aims: We previously reported that patients with moderate-to-severe ulcerative colitis (UC) often experience common mental disorders (CMDs) such as anxiety and depression, necessitating immediate psychological interventions within the first 4 weeks of diagnosis. In this 3-year follow-up study of the MOSAIK cohort in Korea, we examined the effects of CMDs at initial diagnosis on clinical outcomes and health-related quality of life (HRQoL). Methods: We examined differences in clinical outcomes (evaluated based on clinical response, relapse, hospitalization, and medication use) and HRQoL (assessed using the Inflammatory Bowel Disease Questionnaire [IBDQ] and Short Form 12 [SF-12]) according to Hospital Anxiety and Depression Scale (HADS) scores at diagnosis. Results: In a study involving 199 UC patients, 47.7% exhibited significant psychological distress (anxiety and/or depression) at diagnosis. Clinical follow-up showed no major differences in outcomes, including remission rates, response rates, or hospitalization rates, between patients with anxiety or depression at diagnosis and patients without anxiety or depression at diagnosis. The HRQoL at the end of follow-up was notably lower in those with baseline CMDs, particularly anxiety, across all domains of the IBDQ and SF-12. Linear mixed-effect models revealed that higher HADS scores, as well as higher Mayo scores, were independently associated with lower IBDQ scores and both summary domains of the SF-12. Additionally, regular attendance at follow-up visits during the study period was also related to improvements in HRQoL (all p<0.05). Conclusions While CMDs present at the time of UC diagnosis did not influence long-term clinical outcomes, they persistently impaired HRQoL. Our findings support the routine incorporation of psychological interventions into the long-term management of moderate-to-severe UC.

γ-Radiation resistance is a major obstacle to the success of radiotherapy in colorectal cancer. Antioxidant-related factors contribute to resistance to radiation therapy and, therefore, are targets for improving the therapeutic response. In this study, we evaluated the molecular mechanisms underlying γ-radiation resistance using the colorectal cancer cell line SNUC5 and γ-radiation-resistant variant SNUC5/RR, including analyses of the role of nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor that regulates antioxidant enzymes, and related epigenetic regulators. Reactive oxygen species (ROS) levels, antioxidant enzyme expression, NRF2 expression, and nuclear translocation were higher in SNUC5/RR cells irradiated with or without 8 Gy than in SNUC5 cells. The DNA demethylase ten-eleven translocation 1 (TET1) expression and TET1 binding to the NRF2 promoter in SNUC5/RR cells were stronger than those in SNUC5 cells, indicating lower methylation of CpG islands in the NRF2 promoter.TET1 knockdown in SNUC5/RR cells suppressed NRF2 expression significantly. Additionally, histone mixed-lineage leukemia (MLL), a histone methyltransferase, was upregulated, leading to increased trimethylation of histone H3 lysine 4, whereas enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, was downregulated, leading to decreased trimethylation of histone H3 lysine 27. Histone deacetylase (HDAC) and histone acetyltransferase (HAT) levels were lower and higher in SNUC5/RR cells than in SNUC5 cells, respectively. MLL and HAT knockdown in SNUC5/RR cells irradiated with or without 8 Gy decreased levels of NRF2 and heme-oxygenase 1, resulting in enhanced γ-radiation sensitivity. These findings support NRF2 as a target for improving the response to radiotherapy in patients with colorectal cancer.

Purpose: The Korean Cancer Study Group (KCSG) is a nationwide cancer clinical trial group dedicated to advancing investigator-initiated trials (IITs) by conducting and supporting clinical trials. This study aims to review IITs conducted by KCSG and quantitatively evaluate the survival and financial benefits of IITs for patients. Materials and Methods: We reviewed IITs conducted by KCSG from 1998 to 2023, analyzing progression-free survival (PFS) and overall survival (OS) gains for participants. PFS and OS benefits were calculated as the difference in median survival times between the intervention and control groups, multiplied by the number of patients in the intervention group. Financial benefits were assessed based on the cost of investigational products provided. Results: From 1998 to 2023, KCSG conducted 310 IITs, with 133 completed and published. Of these, 21 were included in the survival analysis. The analysis revealed that 1,951 patients in the intervention groups gained a total of 2,558.4 months (213.2 years) of PFS and 2,501.6 months (208.5 years) of OS, with median gains of 1.31 months in PFS and 1.58 months in OS per patient. When analyzing only statistically significant results, PFS and OS gain per patients was 1.69 months and 3.02 months, respectively. Investigational drug cost analysis from six available IITs indicated that investigational products provided to 252 patients were valued at 10,400,077,294 won (approximately 8,046,481 US dollars), averaging about 41,270,148 won (approximately 31,930 US dollars) per patient. Conclusion Our findings, based on analysis of published research, suggest that IITs conducted by KCSG led to survival benefits for participants and, in some studies, may have provided financial benefits by providing investment drugs.

Background/Aims: We previously reported that patients with moderate-to-severe ulcerative colitis (UC) often experience common mental disorders (CMDs) such as anxiety and depression, necessitating immediate psychological interventions within the first 4 weeks of diagnosis. In this 3-year follow-up study of the MOSAIK cohort in Korea, we examined the effects of CMDs at initial diagnosis on clinical outcomes and health-related quality of life (HRQoL). Methods: We examined differences in clinical outcomes (evaluated based on clinical response, relapse, hospitalization, and medication use) and HRQoL (assessed using the Inflammatory Bowel Disease Questionnaire [IBDQ] and Short Form 12 [SF-12]) according to Hospital Anxiety and Depression Scale (HADS) scores at diagnosis. Results: In a study involving 199 UC patients, 47.7% exhibited significant psychological distress (anxiety and/or depression) at diagnosis. Clinical follow-up showed no major differences in outcomes, including remission rates, response rates, or hospitalization rates, between patients with anxiety or depression at diagnosis and patients without anxiety or depression at diagnosis. The HRQoL at the end of follow-up was notably lower in those with baseline CMDs, particularly anxiety, across all domains of the IBDQ and SF-12. Linear mixed-effect models revealed that higher HADS scores, as well as higher Mayo scores, were independently associated with lower IBDQ scores and both summary domains of the SF-12. Additionally, regular attendance at follow-up visits during the study period was also related to improvements in HRQoL (all p<0.05). Conclusions While CMDs present at the time of UC diagnosis did not influence long-term clinical outcomes, they persistently impaired HRQoL. Our findings support the routine incorporation of psychological interventions into the long-term management of moderate-to-severe UC.

Background/Aims: We previously reported that patients with moderate-to-severe ulcerative colitis (UC) often experience common mental disorders (CMDs) such as anxiety and depression, necessitating immediate psychological interventions within the first 4 weeks of diagnosis. In this 3-year follow-up study of the MOSAIK cohort in Korea, we examined the effects of CMDs at initial diagnosis on clinical outcomes and health-related quality of life (HRQoL). Methods: We examined differences in clinical outcomes (evaluated based on clinical response, relapse, hospitalization, and medication use) and HRQoL (assessed using the Inflammatory Bowel Disease Questionnaire [IBDQ] and Short Form 12 [SF-12]) according to Hospital Anxiety and Depression Scale (HADS) scores at diagnosis. Results: In a study involving 199 UC patients, 47.7% exhibited significant psychological distress (anxiety and/or depression) at diagnosis. Clinical follow-up showed no major differences in outcomes, including remission rates, response rates, or hospitalization rates, between patients with anxiety or depression at diagnosis and patients without anxiety or depression at diagnosis. The HRQoL at the end of follow-up was notably lower in those with baseline CMDs, particularly anxiety, across all domains of the IBDQ and SF-12. Linear mixed-effect models revealed that higher HADS scores, as well as higher Mayo scores, were independently associated with lower IBDQ scores and both summary domains of the SF-12. Additionally, regular attendance at follow-up visits during the study period was also related to improvements in HRQoL (all p<0.05). Conclusions While CMDs present at the time of UC diagnosis did not influence long-term clinical outcomes, they persistently impaired HRQoL. Our findings support the routine incorporation of psychological interventions into the long-term management of moderate-to-severe UC.