Platform study of circulating tumor DNA directed adjuvant chemotherapy in colon cancer (CLAUDIA colon cancer, KCSG CO22-12).

Background: Tumor-informed circulating tumor DNA (ctDNA) analysis allows for the sensitive detection of minimal residual disease (MRD) and has the potential to enhance patient stratification for adjuvant chemotherapy. We hypothesize that intensifying adjuvant chemotherapy in colon cancer patients with postoperative MRD positivity may reduce recurrence and improve survival outcomes.

Methods: This multi-center platform trial (NCT05534087) consists of a prospective observational study (Part 1) and an interventional randomized trial (Part 2).

Immunogenomic characteristics and prognostic implications of terminally exhausted CD8 T cells in colorectal cancers.

Introduction: T-cell exhaustion is a major mechanism of immune evasion. Recently, the therapeutic and prognostic implications of progenitor exhausted T cells (Tpex) and terminally exhausted T cells (Ttex) have been explored in various cancer types. This study explored the immunogenomic characteristics and prognostic implications of Tpex and Ttex in colorectal cancers (CRCs).

Clinicopathological and molecular features of genome-stable colorectal cancers.

Colorectal cancers (CRCs) are traditionally divided into those with either chromosomal instability (CIN) or microsatellite instability (MSI). By utilizing TCGA data, the Laird team found a subset of CRCs, namely, genome-stable CRCs (GS CRCs), which lack both CIN and MSI. Although the molecular features of GS CRCs have been described in detail, the clinicopathological features are not well defined.

A Phase 1b/2a Study of GC1118 with 5-Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in Patients with Recurrent or Metastatic Colorectal Cancer.

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.

Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: a phase 1b trial.

KRAS G12C mutation is prevalent in ~4% of colorectal cancer (CRC) and is associated with poor prognosis. Divarasib, a KRAS G12C inhibitor, has shown modest activity as a single agent in KRAS G12C-positive CRC at 400 mg. Epidermal growth factor receptor has been recognized as a major upstream activator of RAS-MAPK signaling, a proposed key mechanism of resistance to KRAS G12C inhibition in CRC.

Single-Agent Divarasib (GDC-6036) in Solid Tumors with a G12C Mutation.

Background: Divarasib (GDC-6036) is a covalent KRAS G12C inhibitor that was designed to have high potency and selectivity.

Methods: In a phase 1 study, we evaluated divarasib administered orally once daily (at doses ranging from 50 to 400 mg) in patients who had advanced or metastatic solid tumors that harbor a G12C mutation. The primary objective was an assessment of safety; pharmacokinetics, investigator-evaluated antitumor activity, and biomarkers of response and resistance were also assessed.

Epigenetic insights into colorectal cancer: comprehensive genome-wide DNA methylation profiling of 294 patients in Korea.

DNA methylation regulates gene expression and contributes to tumorigenesis in the early stages of cancer. In colorectal cancer (CRC), CpG island methylator phenotype (CIMP) is recognized as a distinct subset that is associated with specific molecular and clinical features. In this study, we investigated the genomewide DNA methylation patterns among patients with CRC.

Total neoadjuvant therapy with short-course radiotherapy Versus long-course neoadjuvant chemoradiotherapy in Locally Advanced Rectal cancer, Korean trial (TV-LARK trial): study protocol of a multicentre randomized controlled trial.

Background: For locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT) may enhance tumour response, reduce recurrence, and improve patient compliance compared to upfront surgery. Recent studies have shown that chemoradiotherapy (CRT) followed by consolidation chemotherapy leads to higher rate of pathologic complete response (pCR) than induction chemotherapy followed by CRT. However, an optimal TNT regimen that maximise the pCR rate and minimise toxicity has not been established.

Predicting the chemotherapeutic response of colorectal cancer liver metastasis using shear-wave elastography.

Purpose: The aim of this study was to assess the role of the shear-wave velocity (SWV) value in predicting chemotherapeutic response and progression-free survival (PFS) in patients with colorectal cancer liver metastasis (CRLM).

Methods: In this prospective single-center study, participants with CRLM scheduled for chemotherapy were enrolled between May 2018 and June 2021. SWV measurements were obtained using shear-wave elastography at the CRLM site before and after initiating chemotherapy.

Personalised circulating tumour DNA assay with large-scale mutation coverage for sensitive minimal residual disease detection in colorectal cancer.

Background: Postoperative minimal residual disease (MRD) detection using circulating-tumour DNA (ctDNA) requires a highly sensitive analysis platform. We have developed a tumour-informed, hybrid-capture ctDNA sequencing MRD assay.

Methods: Personalised target-capture panels for ctDNA detection were designed using individual variants identified in tumour whole-exome sequencing of each patient.

Mutational evolution after chemotherapy-progression in metastatic colorectal cancer revealed by circulating tumor DNA analysis.

Emerging new mutations after treatment can provide clues to acquired resistant mechanisms. Circulating tumor DNA (ctDNA) sequencing has enabled noninvasive repeated tumor mutational profiling. We aimed to investigate newly emerging mutations in ctDNA after disease progression in metastatic colorectal cancer (mCRC).

Circulating Tumor DNA Dynamics and Treatment Outcome of Regorafenib in Metastatic Colorectal Cancer.

Purpose: Circulating tumor DNA (ctDNA) is emerging as a valuable non-invasive tool to identify tumor heterogeneity and tumor burden. This study investigated ctDNA dynamics in metastatic colorectal cancer patients treated with regorafenib.

Materials And Methods: In this prospective biomarker study, plasma cell-free DNA (cfDNA) samples obtained at baseline, at the first response evaluation after 2 cycles of treatment, and at the time of progressive disease were sequenced using a targeted next-generation sequencing platform which included 106 genes.

Utilizing Plasma Circulating Tumor DNA Sequencing for Precision Medicine in the Management of Solid Cancers.

Plasma circulating tumor DNA (ctDNA) sequencing has demonstrated clinical utility for tumor molecular profiling at initial diagnosis or tumor progression in advanced solid cancers and is being rapidly incorporated into the clinical practice guidelines, including non-small cell lung and breast cancer. Despite relatively low sensitivity, plasma ctDNA sequencing has several advantages over tissue-based assays, including ease of sampling, rapid turnaround time, repeatability, and the ability to overcome spatial heterogeneity, which makes it ideal for investigating acquired resistance and monitoring tumor evolution and dynamics. With technological advancement and declining costs, the clinical application of plasma ctDNA is expanding, and numerous ongoing clinical trials are examining its potential to guide the management of advanced, localized, and even preclinical cancers of various tumor types.

Destabilizing NF1 variants act in a dominant negative manner through neurofibromin dimerization.

The majority of pathogenic mutations in the neurofibromatosis type I () gene reduce total neurofibromin protein expression through premature truncation or microdeletion, but it is less well understood how loss-of-function missense variants drive NF1 disease. We have found that patient variants in codons 844 to 848, which correlate with a severe phenotype, cause protein instability and exert an additional dominant-negative action whereby wild-type neurofibromin also becomes destabilized through protein dimerization. We have used our neurofibromin cryogenic electron microscopy structure to predict and validate other patient variants that act through a similar mechanism.

A Phase II Trial of S-1 and Oxaliplatin in Patients with Metastatic Breast Cancer Previously Treated with Anthracycline and Taxane (KCSG-BR07-03).

Purpose: This single-arm phase II trial investigate the efficacy and safety of S-1 plus oxaliplatin (SOX) in patients with metastatic breast cancer.

Materials And Methods: Patients with metastatic breast cancer previously treated with anthracyclines and taxanes were enrolled. Patients received S-1 (40-60 mg depending on patient's body surface area, twice a day, day 1-14) and oxaliplatin (130 mg/m2, day 1) in 3 weeks cycle until disease progression or unacceptable toxicity.

Standard versus longer interval of radical resection after neoadjuvant chemoradiotherapy in locally advanced rectal cancer: A 20-year single-center experience & propensity-score matching.

Background And Objectives: Despite the standard interval of 6-8 weeks between neoadjuvant chemoradiotherapy (nCRT) and surgery, it is debated whether an interval of >8 weeks increases the pathologic complete response (pCR) rate. We investigated the interval between nCRT and surgery, and its impact on oncological outcomes and postoperative complications in patients with locally advanced rectal cancer.

Methods: We retrospectively reviewed patients with rectal cancer who underwent total mesorectal excision after long-course nCRT between 2000 and 2020.

Preclinical Characterization and Phase I Study of an Anti-HER2-TLR7 Immune-Stimulator Antibody Conjugate in Patients with HER2+ Malignancies.

Immune-stimulator antibody conjugates (ISAC) combining tumor-targeting monoclonal antibodies with immunostimulatory agents allow targeted delivery of immune activators into tumors. NJH395 is a novel, first-in-class ISAC comprising a Toll-like receptor 7 (TLR7) agonist conjugated to an anti-HER2 antibody via a noncleavable linker payload. Preclinical characterization showed ISAC-mediated activation of myeloid cells in the presence of antigen-expressing cancer cells, with antigen targeting and TLR7 agonism contributing to antitumor activity.

Phase 1 Study of No-Carrier Added 177Lu-DOTATATE (SNU-KB-01) in Patients with Somatostatin Receptor-Positive Neuroendocrine Tumors: The First Clinical Trial of Peptide Receptor Radionuclide Therapy in Korea.

Purpose: To provide a wider choice of treatment opportunities for patients with neuroendocrine tumor (NET) in Korea, we have conducted a phase 1, open-label, single-arm, dose-escalation study of SNU-KB-01, a no-carrier added (NCA) 177Lu-labeled DOTATATE.

Materials And Methods: Seven patients with inoperable, progressive, metastatic, or locally advanced, somatostatin receptor-positive NET with Ki67 index ≤ 20% were enrolled according to the rolling six design. The study consisted of two cohorts to receive 4 cycles of SNU-KB-01 every 8 weeks for the first dose of 5.

Role of Dedicated Subspecialized Radiologists in Multidisciplinary Team Discussions on Lower Gastrointestinal Tract Cancers.

Objective: To determine the impact of dedicated subspecialized radiologists in multidisciplinary team (MDT) discussions on the management of lower gastrointestinal (GI) tract malignancies.

Materials And Methods: We retrospectively analyzed the data of 244 patients (mean age ± standard deviation, 61.7 ± 11.

Safety and effectiveness of aflibercept in combination with FOLFIRI in Korean patients with metastatic colorectal cancer who received oxaliplatin-containing regimen.

Purpose: To evaluate the safety and effectiveness of aflibercept in combination with fluorouracil, leucovorin, and irinotecan (FOLFIRI) in Korean patients with metastatic colorectal cancer (mCRC) who progressed with oxaliplatin-containing regimen.

Methods: This was a prospective observational study conducted at 22 sites across Korea between February 2018 and September 2019. Patients aged > 19 years with a diagnosis of mCRC who were prescribed aflibercept plus FOLFIRI, after progression with an oxaliplatin-containing regimen were included.

Prognostic Impact of Extramural Lymphatic, Vascular, and Perineural Invasion in Stage II Colon Cancer: A Comparison With Intramural Invasion.

Background: Lymphatic invasion, vascular invasion, and perineural invasion are prognostic factors for colon cancer. However, the prognostic significance of those factors according to the location of permeation (intramural and extramural invasion) in stage II colon cancer is still unclear.

Objective: This study aimed to clarify whether the location of lymphatic invasion, vascular invasion, and perineural invasion could affect the survival of patients with stage II colon cancer.