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In recent years, next-generation sequencing (NGS)-based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Background: Next-generation sequencing (NGS) has been introduced to many Korean institutions to support molecular diagnostics in cancer since 2017, when it became eligible for reimbursement by the National Health Insurance Service. However, the uptake of molecularly guided treatment (MGT) based on NGS results has been limited because of stringent regulations regarding prescriptions outside of approved indications, a lack of clinical trial opportunities, and limited access to molecular tumor boards (MTB) at most institutions. The KOSMOS-II study was designed to demonstrate the feasibility and effectiveness of MGT, informed by MTBs, using a nationwide precision medicine platform., Methods: The KOSMOS-II trial is a large-scale nationwide master observational study. It involves a framework for screening patients with metastatic solid tumors for actionable genetic alterations based on local NGS testing. It recommends MGT through a remote and centralized MTB meeting held biweekly. MGT can include one of the following options: Tier 1, the therapeutic use of investigational drugs targeting genetic alterations such as ALK, EGFR, ERBB2, BRAF, FH, ROS1, and RET, or those with high tumor mutational burden; Tier 2, comprising drugs with approved indications or those permitted for treatment outside of the indications approved by the Health Insurance Review and Assessment Service of Korea; Tier 3, involving clinical trials matching the genetic alterations recommended by the MTB. Given the anticipated proportion of patients receiving MGT in the range of 50% ± 3.25%, this study aims to enroll 1,000 patients. Patients must have progressed to one or more lines of therapy and undergone NGS before enrollment., Discussion: This pragmatic master protocol provides a mass-screening platform for rare genetic alterations and high-quality real-world data. Collateral clinical trials, translational studies, and clinico-genomic databases will contribute to generating evidence for drug repositioning and the development of new biomarkers., Trial Registration: NCT05525858., (© 2024. The Author(s).)

Purpose: Tropomyosin receptor kinase (TRK) inhibitors are approved for the treatment of neurotrophic receptor tyrosine kinase (NTRK) fusion-positive tumors. The detection of NTRK fusion using a validated method is required before therapeutic application. An interlaboratory comparison study of next-generation sequencing (NGS)-based NTRK gene fusion detection with validated clinical samples was conducted at six major hospitals in South Korea., Materials and Methods: A total of 18 samples, including a positive standard reference and eight positive and nine negative clinical samples, were validated using the VENTANA pan-TRK (EPR17341) and TruSight Oncology 500 assays. These samples were then tested using four different NGS panels currently being used at the six participating institutions., Results: NTRK fusions were not detected in any of the nine negative clinical samples, demonstrating 100% specificity in all six participating institutions. All assays showed 100% analytical sensitivity to identify the NTRK fusion status in formalin-fixed paraffin-embedded (FFPE) samples, although with variable clinical sensitivity. False-negative results were due to low tumor purity, poor RNA quality, and DNA-based sequencing panel. The RNA-based targeted NGS assay showed an overall high success rate of identifying NTRK fusion status in FFPE samples., Conclusion: This study is the first to test the proficiency of NGS-based NTRK detection in South Korea with the largest participating institutions. RNA-based NGS assays to detect NTRK fusions can accurately characterize fusion transcripts if sufficient RNA of adequate quality is available. The comparative performance data will support the implementation of targeted NGS-based sequencing assays for NTRK fusion detection in routine diagnostics.

Background: TP53 is the most frequently mutated gene in the human cancer, and the awareness of its mutational status is useful in the diagnosis and treatment of cancer patients. In the present study, we investigated the association between TP53 gene mutations and p53 immunohistochemical staining (IHC) patterns and non-genetic effect of MDM2 as a negative regulator of p53., Methods: A total of 135 solid cancer cases with next generation sequencing data were subjected to p53 IHC and classified as overexpression, null type or usual pattern., Results: TP53 mutation was observed in 104 out of 135 cases (77.0%). When the TP53 mutations were annotated into DISRUPTED (truncations, frameshifts, splice site mutations, and deep deletions) and IF-DBD (in-frame mutations in the DNA binding domain), the null type p53 IHC pattern was associated with DISRUPTED mutations (sensitivity 86.2%, specificity 97.2%) while the overexpression pattern was associated with IF-DBD mutations (sensitivity 100%, specificity 81.7%). The specificity of p53 IHC usual pattern predicting wild type TP53 was also as high as 100%. Regardless of MDM2 amplification, p53 IHC pattern showed a perfect association with TP53 mutation pattern., Conclusions: p53 IHC pattern (overexpression, null type, usual) reasonably predicted TP53 mutational status (DISRUPTED, IF-DBD), and MDM2 amplification status did not have any impact on the p53 IHC pattern., (© 2022. The Author(s).)

Predicting the radiation dose‒toxicity relationship is important for local tumor control and patients' quality of life. We developed a first intuitive evaluation system that directly matches the three-dimensional (3D) dose distribution with the skin surface image of patients with radiation dermatitis (RD) to predict RD in patients undergoing radiotherapy. Using an RGB-D camera, 82 3D skin surface images (3DSSIs) were acquired from 19 patients who underwent radiotherapy. 3DSSI data acquired included 3D skin surface shape and optical imaging of the area where RD occurs. Surface registration between 3D skin dose (3DSD) and 3DSSI is performed using the iterative closest point algorithm, then reconstructed as a two-dimensional color image. The developed system successfully matched 3DSSI and 3DSD, and visualized the planned dose distribution onto the patient's RD image. The dose distribution pattern was consistent with the occurrence pattern of RD. This new approach facilitated the evaluation of the direct correlation between skin-dose distribution and RD and, therefore, provides a potential to predict the probability of RD and thereby decrease RD severity by enabling informed treatment decision making by physicians. However, the results need to be interpreted with caution due to the small sample size., (© 2022. The Author(s).)

Next-generation sequencing (NGS) is becoming essential in the fields of precision oncology. With implementation of NGS in daily clinic, the needs for continued education, facilitated interpretation of NGS results and optimal treatment delivery based on NGS results have been addressed. Molecular tumor board (MTB) is multidisciplinary approach to keep pace with the growing knowledge of complex molecular alterations in patients with advanced solid cancer. Although guidelines for NGS use and MTB have been developed in western countries, there is limitation for reflection of Korea's public health environment and daily clinical practice. These recommendations provide a critical guidance from NGS panel testing to final treatment decision based on MTB discussion.

Purpose: With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data., Materials and Methods: To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared., Results: We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration., Conclusion: In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.

We report a multimodal biomicroscopic system which offers high-frequency ultrasound B-mode, acoustic radiation force impulse (ARFI), and multispectral imaging for qualitative tumor characterization ex vivo. Examinations of resected tissues from diseased regions such as tumors are crucial procedures during surgical operations to treat cancer. Particularly, if tiny tumors remain at surgical sites after tumor resection, such tumors can result in unwanted outcomes, such as cancer recurrence or metastasis to other organs. To avoid this, accurate characterizations of tumors resected during surgery are necessary. To this end, we devised a multimodal biomicroscopic system including high-frequency ultrasound B-mode, ARFI, and multispectral imaging modalities to examine resected tumors with high levels of accuracy. This system was evaluated with tissue-mimicking phantoms with different mechanical properties. In addition, colorectal tumors excised from cancer patients were examined. The proposed system offers highly resolved anatomical, mechanical, chemical information pertaining to tumors, thus allowing the detection of tumor regions from the surface to deep inside tissues. These results therefore suggest that the multimodal biomicroscopic system has the potential to undertake qualitative characterizations of excised tumors ex vivo.