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Background: Oenanthe javanica (Blume) DC., also known as water dropwort, is an aquatic plant species native to various regions across Asia. Despite its numerous health-promoting effects, research on improving its quality remains limited. The present study aimed to identify the optimal soil conditions required for high-quality water dropwort production., Results: Fifty crop and soil samples from South Korean farms were analyzed for their functional content, soil chemical properties and plant tissue components. The results indicated that crop samples with lower functional components had higher soil pH, electrical conductivity (EC) and exchangeable cations than those with higher functional components. High-quality crop samples exhibited neutral soil pH and low EC values, suggesting better nutrient availability for crop growth and reduced salt stress as a result of mineral accumulation in soil., Conclusion: These findings suggest that soils affected by excessive salinity may create suboptimal soil conditions for water dropwort cultivation, potentially compromising crop quality. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

Background: Antipsychotic drugs (APDs) are used for treating mental illnesses and are also used by cancer patients. This study aimed to evaluate APD use in adult cancer patients who received radiotherapy (RT) in South Korea and assess the effects of APD use during RT on survival., Methods: This retrospective cohort study utilized the National Health Insurance Service database database of Korea. We included adult cancer patients who underwent RT or chemotherapy (CTx, cisplatin, or 5-Fluorouracil) between 2010 and 2020. The APDs included in the analysis were aripiprazole, quetiapine, olanzapine, risperidone, haloperidol, and chlorpromazine., Results: Overall, 725,897 patients received RT, and 115,500 received concomitant chemo-radiotherapy (CCRT). Of them, 41,118 (5.6%) took APDs during RT, and 8,129 (7%) took APDs during CCRT. Overall, 27,789 (67.58%) patients who took APDs during RT were men, and 28,004 (68.2%) were aged ≥ 60 years. The most frequently used APD during RT was quetiapine (64.93%). Patients who took APDs during RT and during CCRT had higher mortality rates (HR: 3.45 and 1.72, p < 0.0001, respectively) compared to the non-APD patients. Of the patients who used APDs during RT, patients accompanying psychiatric diagnosis, taking high-dose APD, and taking APD for more than 3 months had lower mortality than patients without psychiatric diagnosis, taking low-dose APD, and taking APD for less than 3 months, respectively (HR: 0.88, 0.87 and 0.80, respectively, p < 0.0001)., Conclusions: Only 5.6% of patients who underwent RT used APDs, and quetiapine was the most frequently prescribed APD during RT. The use of APD during RT may adversely affect survival. Further studies are required to elucidate the effects of APDs on cancer patients., Trial Registration: This study is retrospectively registered., Competing Interests: Declarations. Ethics approval and consent to participate: This study was performed after approval from the Institutional Review Boards of Chung-Ang University Hospital (CAUH IRB No.2202-022-19407). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

In this study, we aimed to investigate the nationwide utilization of antipsychotic drugs (APDs) during radiotherapy and evaluate their association with survival in patients with breast cancer. This retrospective cohort study used the National Health Insurance Service database in Korea and included patients diagnosed with breast cancer from 2010 to 2020 who received radiotherapy. The APDs included in the analysis were aripiprazole, quetiapine, olanzapine, risperidone, haloperidol, and chlorpromazine, and the APD prescription details included prescription time, dosage, and duration. Among 170,226 patients with breast cancer treated with radiotherapy, 3361 (1.97%) received APD during radiotherapy. Use of APDs was significantly associated with higher mortality in all patients and in a subgroup of patients excluding those with metastasis or other cancers. Among patients taking APD during radiotherapy, those with accompanied psychiatric history and long-term APD use for ≥ 3 months were associated with lower mortality, whereas patients who started APD during radiotherapy had higher mortality than those who started APD before radiotherapy. The high mortality observed in breast cancer patients using APDs during radiotherapy could be influenced by the underlying conditions that necessitated APD use. Further studies are needed to determine the effects of APDs during radiotherapy in patients with breast cancer., (© 2024. The Author(s).)

Background: The physical dependence on prescription opioids among cancer survivors remains an under-investigated area, with a scarcity of well-designed prospective studies., Methods: This single-arm, phase-2 clinical trial in Korea assessed the efficacy and safety of a transdermal buprenorphine patch (TBP) in managing physical dependence on prescription opioids in cancer survivors, as confirmed through the DSM-5 criteria or psychiatric consultation for opioid withdrawal. This study involved a 4-phase treatment protocol of screening, induction/stabilization, discontinuation, and monitoring. The primary outcome was the rate of successful opioid discontinuation, as measured by a negative urine-drug screening at 8 weeks. Key secondary outcomes included the resumption of prescribed opioids, changes in both the Clinical Opioid Withdrawal Scale (COWS) and morphine equivalent daily dose (MEDD), and assessments related to the psychological and physiological aspects of dependence and safety., Results: Thirty-one participants were enrolled. In the intention-to-treat population, the success rate of opioid discontinuation was 58%, with only 2 participants experiencing a resumption of prescribed opioids. Significant reductions were observed in MEDD, which decreased from 98 to 26 mg/day (P < .001), and COWS scores, which decreased from 5.5 to 2.8 (P < .001). Desire to use opioids reduced from 7.0 to 3.0 on a 10-point numeric rating scale (P < .001). Toxicities related to TBP were mild and manageable, without severe precipitated withdrawal symptoms., Conclusion: TBP may be considered as an alternative therapeutic option in cancer survivors physically dependent on prescription opioids, especially where sublingual formulations are unavailable., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Next-generation sequencing (NGS) has become widely available but molecular profiling-guided therapy (MGT) had not been well established in the real world due to lack of available therapies and expertise to match treatment. Our study was designed to test the feasibility of a nationwide platform of NGS-guided MGT recommended by a central molecular tumor board (cMTB) for metastatic solid tumors., Patients and Methods: Patients with advanced or metastatic solid tumors with available NGS results and without standard treatment were enrolled. The cMTB interpreted the patients' NGS reports and recommended the following: (i) investigational medicinal products (IMPs) approved in other indications; (ii) alternative treatments; (iii) clinical trials. The primary variables were the proportion of patients with actionable genomic alterations and those receiving MGT as per cMTB recommendations. Others included treatment duration (TD), overall response rate (ORR), disease control rate (DCR), and safety., Results: From February 2021 to February 2022, 193 cases [99 (51.3%) men; median age 58 years (range 24-88 years); median line of previous treatment 3 (range 0-9)] from 29 sites were enrolled for 60 cMTB sessions. The median time from case submission to cMTB discussion was 7 days (range 2-20 days), and to IMP treatment initiation was 28 days (range 14-90 days). Actionable genetic alterations were found in 145 patients (75.1%). A total of 89 (46.1%) patients received actual dosing of IMPs, and 10 (5.2%) were enrolled in cMTB-recommended clinical trials, achieving an MGT rate of 51.3%. ORR and DCR of IMPs were 10.1% and 72.5%, respectively. The median TD was 3.5 months [95% confidence interval (CI) 2.8-5.5 months], and the 4-month TD rate was 44.9%. The median overall survival of patients who received IMPs was 6.9 months (95% CI 5.2-10.0 months)., Conclusion: KOSMOS confirmed the feasibility of MGT recommended by the cMTB, achieving a high MGT match rate and promising effectiveness in heavily pretreated advanced cancer patients., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This study was conducted to evaluate the effects of Allium hookeri (AH) leaves cultivated with different light-emitting diode (LED) intensities (L: low, 100 μmol/m 2 /s; M: medium, 150 μmol/m 2 /s; H: high, 200 μmol/m 2 /s). Alliin concentration increased as light intensity increased in AH and showed the highest level at LED-H condition. The anti-obesity and immunomodulatory properties of AH were evaluated in a cyclophosphamide (CPA)-induced immunosuppressed obese animal model. C57BL/6 J mice were randomly divided into control (CON), high-fat diet (HFD) control (CON-H), negative control (NC), positive control (PC, β-glucan, 50 mg/kg body weight (BW)), AH L, M, and H groups. The three kinds of AH extracts were orally administered to the mice at 300 mg/kg BW for 2 weeks. Except for CON and CON-H, all the other groups were intraperitoneally treated with CPA. Epididymal and abdominal fat weight decreased as LED intensity increased while spleen weight increased in the AH groups. Serum glucose decreased as LED intensity increased in the AH groups and H group showed the lowest level. Triglycerides, total, and LDL-cholesterol levels decreased while HDL-cholesterol level increased in the AH groups compared to the NC group. Moreover, AH effectively reduced serum ALT and AST levels and increased the total white blood cell count, particularly elevating lymphocyte and monocyte levels. Furthermore, NK cell activity was higher in the AH groups. These findings suggest that AH cultivated at optimal LED intensity could be used as a novel biomedicine and in pharmacotherapy to treat related diseases to improve public health without any toxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background/objectives: Obesity, characterized by abnormal fat accumulation and metabolic disturbances, presents a significant health challenge. Opuntia humifusa Raf., commonly known as Korean Cheonnyuncho, is rich in various beneficial compounds and has demonstrated antioxidant and anti-inflammatory effects. However, its potential impact on glucose and lipid metabolism, particularly in obese rats, remains unexplored. We aimed to investigate whether O. humifusa stems and fruits could beneficially alter glucose metabolism and lipid profiles in a rat model of high-fat diet (HFD)-induced obesity., Materials/methods: Thirty-two rats were allocated into 4 groups: normal diet (NF), HFD control (HF), HFD treated with 2% O. humifusa stems (HF-OS), and HFD treated with 2% O. humifusa fruits (HF-OF). Experimental diets were administered for 6 weeks. At the end of the treatment, liver and fat tissues were isolated, and serum was collected for biochemical analysis. The major flavonoid from O. humifusa stems and fruits was identified and quantified., Results: After 6 weeks of treatment, the serum fasting glucose concentration in the HF-OS group was significantly lower than that in the HF group. Serum fasting insulin concentrations in both HF-OS and HF-OF groups tended to be lower than those in the HF group, indicating a significant improvement in insulin sensitivity in the HF-OS group. Additionally, the HF-OS group exhibited a tendency towards the restoration of adiponectin levels to that of the NF group., Conclusion: The 2% O. humifusa stems contain abundant quercetin and isorhamnetin, which alter fasting blood glucose levels in rats fed a HFD, leading to a favorable improvement in insulin resistance., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interests., (©2024 The Korean Nutrition Society and the Korean Society of Community Nutrition.)

Backgrounds/aims: Reported incidence of extrahepatic bile duct cancer is higher in Asians than in Western populations. Korea, in particular, is one of the countries with the highest incidence rates of extrahepatic bile duct cancer in the world. Although research and innovative therapeutic modalities for extrahepatic bile duct cancer are emerging, clinical guidelines are currently unavailable in Korea. The Korean Society of Hepato-Biliary-Pancreatic Surgery in collaboration with related societies (Korean Pancreatic and Biliary Surgery Society, Korean Society of Abdominal Radiology, Korean Society of Medical Oncology, Korean Society of Radiation Oncology, Korean Society of Pathologists, and Korean Society of Nuclear Medicine) decided to establish clinical guideline for extrahepatic bile duct cancer in June 2021., Methods: Contents of the guidelines were developed through subgroup meetings for each key question and a preliminary draft was finalized through a Clinical Guidelines Committee workshop., Results: In November 2021, the finalized draft was presented for public scrutiny during a formal hearing., Conclusions: The extrahepatic guideline committee believed that this guideline could be helpful in the treatment of patients.

Advancements in the treatment and management of patients with cancer have extended their survival period. To honor such patients' desire to live in their own homes, home-based supportive care programs have become an important medical practice. This study aims to investigate the effects of a multidimensional and integrated home-based supportive care program on patients with advanced cancer. SupporTive Care At Home Research is a cluster non-randomized controlled trial for patients with advanced cancer. This study tests the effects of the home-based supportive care program we developed versus standard oncology care. The home-based supportive care program is based on a specialized home-based medical team approach that includes (1) initial assessment and education for patients and their family caregivers, (2) home visits by nurses, (3) biweekly regular check-ups/evaluation and management, (4) telephone communication via a daytime access line, and (5) monthly multidisciplinary team meetings. The primary outcome measure is unplanned hospitalization within 6 months following enrollment. Healthcare service use; quality of life; pain and symptom control; emotional status; satisfaction with services; end-of-life care; advance planning; family caregivers' quality of life, care burden, and preparedness for caregiving; and medical expenses will be surveyed. We plan to recruit a total of 396 patients with advanced cancer from six institutions. Patients recruited from three institutions will constitute the intervention group, whereas those recruited from the other three institutions will comprise the control group., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Immune-modulating antibodies targeting programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) have demonstrated promising antitumor efficacy in various types of cancers, especially highly mutated ones. Genetic alterations in DNA damage response and repair (DDR) genes can lead to genetic instability, often accompanied by a high tumor mutation burden (TMB). However, few studies have validated the aberration of DDR genes as a predictive biomarker for response to immune-modulating antibodies., Methods: The KM-06 open-label, multicenter, single-arm, phase II trial evaluated the safety and efficacy of nivolumab in refractory solid cancers with DDR gene mutations assessed by clinically targeted sequencing. Nivolumab (3 mg/kg) was administered every 2 weeks until disease progression, unacceptable toxicity, or for 24 months. The primary endpoint was the objective response rate (ORR) as per RECIST V.1.1 criteria., Results: A total of 48 patients were enrolled in the study (median age 61, 58.3% male). The most common cancer type was colorectal cancer (41.7%), followed by prostate and biliary tract cancer (8.3% each). Eight patients achieved a partial response as their best overall response, resulting in an ORR of 17.8%. The disease control rate was 60.0%. The median progression-free survival was 2.9 months. Treatment-related adverse events of any grade and grade ≥3 occurred in 44 (91.7%) and 4 (8.3%) patients, respectively. Clinically targeted sequencing data inferred both TMB and microsatellite instability (MSI). Using a TMB cut-off of 12 mut/Mb, there were significant differences in overall survival (p=0.00035), progression-free survival (p=0.0061), and the best overall response (p=0.05). In the RNA sequencing analysis, nivolumab responders showed activation of the interleukin signaling pathway. Patients who experienced early progression presented high epithelial-mesenchymal transition signaling pathway activation. The responders exhibited a marked increase in PD-1-/Ki67+CD8 T cells at the early stage of treatment (C3D1) compared with non-responders (p=0.03)., Conclusions: In this phase II trial, nivolumab demonstrated moderate efficacy and manageable toxicity in patients with solid cancer harboring DDR gene mutations. A high TMB (>12 mut/Mb) and MSI score (>2.5) determined through clinically target sequencing presented significant discriminatory power for the nivolumab response., Trial Registration Number: NCT04761744., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: This study aimed to screen targeted agents as second-line treatment with a standard-of-care (SOC) controlled umbrella trial design in advanced gastric cancer (AGC)., Patients and Methods: Patients with HER2-negative AGC from eight Korean cancer centers were screened for druggable targets using immunohistochemistry (IHC) and in situ hybridization, and randomly assigned to the biomarker versus control group at a 4:1 ratio. In the biomarker group, patients were treated with specific targeted agent plus paclitaxel: pan-ERBB inhibitor for epidermal growth factor receptor (EGFR) 2+/3+ patients (afatinib; EGFR cohort), PIK3Cβ inhibitor for phosphatase and tensin homolog (PTEN) loss/null patients (GSK2636771; PTEN cohort), and anti-PD-1 inhibitor for PD-L1+, deficient mismatch repair/microsatellite instability-high, or Epstein-Barr virus-related cases (nivolumab; NIVO cohort). NONE cohort in the biomarker group without predefined biomarkers and control group received SOC (paclitaxel with or without ramucirumab). The primary end point was progression-free survival (PFS), and the secondary end points were efficacy and safety., Results: A total of 318 patients were randomly assigned into the control (n = 64) and biomarker (n = 254; EGFR, n = 67; PTEN, n = 37; NIVO, n = 48; NONE, n = 102) groups. Median follow-up was 35 months. Median PFS and overall survival (OS) were 3.7 (95% CI, 3.1 to 4.1) and 8.6 (95% CI, 7.6 to 9.8) months in the biomarker group and 4.0 (95% CI, 3.0 to 4.6) and 8.7 (95% CI, 7.1 to 9.9) months in the control group. Afatinib addition led to marginal survival benefits to patients with EGFR 3+ compared with SOC (PFS, 4.0 v 2.2 months; P = .09), but GSK2636771 did not prolong the survival of patients with PTEN loss. Addition of nivolumab showed a durable survival benefit (median OS, 12.0 v 7.6 months; P = .08)., Conclusion: Although biomarker group did not show better survival than the control group, IHC-based screening and allocation of patients with AGC to the second-line treatment in an umbrella design were feasible for effective early screening of novel agents.

We investigated the immune-stimulating and anti-diabetic effects of Allium hookeri leaves grown in a plant factory with artificial lights. The immunomodulatory effects of A. hookeri leaves' ethanol extracts were evaluated with immune-related hematological factors in blood, the proliferation of splenocytes, NK cell activity, IgG and cytokine levels, and their mechanisms in immunosuppressed obese mice. Anti-diabetic effects were determined by the inhibitory activity against α-amylase and α-glucosidase in vitro and fasting blood glucose levels and biochemical factors in the serum of immunosuppressed obese mice. A. hookeri leaf extracts increased WBC and LYM counts, the proliferation of splenocytes, and serum IgG and IL-1β concentrations compared to those of the NC group, which was used as a negative control. A. hookeri leaf extracts also improved serum HDL levels while they decreased the activities of digestive enzymes, fasting blood glucose, and biochemical factors (ALT, AST, T-Chol, TG, LDL, and GLU). The expressions of IL-1β, JNK, c-Jun, p65, and iNOS in the thymus of immunosuppressed mice were activated by the treatment of A. hookeri leaf extracts. The results suggest that A. hookeri leaves grown in a plant factory with artificial lights also have immune-stimulatory and anti-diabetic effects and can be used as novel functional supplements to control related diseases and to improve public health.

Background/aim: This study investigated the treatment patterns and prognosis of patients with metastatic or unresectable colorectal cancer (mCRC) treated with chemotherapy with targeting agents., Patients and Methods: This longitudinal multicenter study included 963 patients with mCRC who were treated in Korea between 2016 and 2020. Treatment patterns and efficacy were compared according to the mutation status and clinical factors., Results: As first-line therapy, most of the patients (83.5%) received FOLFOX plus bevacizumab (35.4%), followed by FOLFIRI plus bevacizumab (18.8%), FOLFIRI plus cetuximab (17.0%), and FOLFOX plus cetuximab (12.3%). Bevacizumab was the most frequent agent (78.8%) combined with chemotherapy in RAS-mutated CRC, while cetuximab (57.2%) in RAS wild-type CRC. Cetuximab was frequently combined with a doublet regimen in patients with left-sided CRC than in those with right-sided CRC (34.4% vs. 16%). As second-line therapy, most patients (63.4%) also received doublet regimens with bevacizumab, and FOLFIRI plus aflibercept was administered in 15.1%. The objective response rate with FOLFIRI plus cetuximab was significantly higher in patients with left-sided CRC than in those with right-sided CRC (59.2% vs. 30.8%, p=0.008) and marginally higher in patients with RAS wild-type CRC than in those with RAS-mutated CRC (55.6% vs. 0.0%, p=0.092). Progression-free survival (PFS) with FOLFOX plus bevacizumab was significantly shorter than that with FOLFIRI plus bevacizumab (p=0.030) in RAS-mutated CRC, whereas there were no significant differences between regimens in RAS wild-type CRC., Conclusion: In patients with unresectable metastatic colorectal cancer, doublet chemotherapy with targeting agents is the most common therapy and efficacy depends on the mutation status as well as clinical factors., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: We conducted a trial to evaluate the efficacy and safety of nivolumab and paclitaxel as second-line therapy for immune-related biomarker-enriched advanced gastric cancer (AGC)., Methods: This open-label, single-arm, phase Ib/II study was a part of multi-institutional, biomarker-integrated umbrella study conducted in Korea. In phase Ib, patients received nivolumab (3 mg/kg) on Days 1 and 15 and paclitaxel (dose level 1, 70 mg/m 2 or dose level 2, 80 mg/m 2 ) on Days 1, 8, 15 every four weeks. In phase II, patients with Epstein-Barr virus-related, deficient mismatch repair or programmed cell death-ligand-1-positive AGC were enrolled. The primary endpoints were recommended phase II dose (RP2D, phase Ib) and progression-free survival (PFS, phase II). Secondary endpoints included objective response rate (ORR), overall survival (OS), safety, and exploratory biomarker analysis., Results: Dose level 2 was selected as RP2D. In phase II, 48 patients were enrolled. The median PFS and OS were 3.9 and 11.2 months, respectively. The ORR was 23.3%, and the median response duration was 16.7 months. Grade 3 or higher treatment-related adverse events, mainly neutropenia, occurred in 20 patients (41.7%). Targeted sequencing revealed that patients with RTK/RAS pathway alterations or the HLA-A02 supertype had better survival. Patients with elevated baseline interleukin-1 receptor antagonist levels had worse survival., Conclusions: Although the study did not meet its primary end point, nivolumab and paclitaxel for AGC demonstrated a durable response with manageable toxicity profiles. Genomic analysis or plasma cytokine analysis may provide information for the selection of patients who would benefit more from immunotherapy combined with chemotherapy., (© 2023. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)

Introduction: Tannin content and postharvest quality characteristics of persimmon fruit are often determined by the destructive analysis that consumes time, does not allow the acquisition of data from the same fruit continuously, and requires expensive high-performance equipment. This research was done to investigate the potential for non-destructive estimation of astringency and quality parameters in persimmon fruit based on visible/near-infrared (VNIR) spectra., Methods: VNIR spectra readings, the reference tannin content, and quality parameters were measured from fruits of "Cheongdo-Bansi" and "Daebong" persimmon cultivars at harvest and throughout the ripening/deastringency period. The spectra readings from half of the total fruit were utilized for the calibration set, while the other half readings were used for the prediction set. To develop models correlating the spectra data to the measured reference parameters data, the partial least square regression (PLSR) method was utilized., Results and Discussion: In the case of 'Daebong', the coefficients of determination (R 2 ) between VNIR spectra and the actual measured values of TSS, firmness, simple sugars, and tannin content were (0.95, 0.94, 0.96, and 0.96) and (0.93, 0.89, 0.96, and 0.93), for the calibration and prediction sets, respectively. Similarly, the R 2 -values of (0.86, 0.93, 0.79, and 0.81) and (0.83, 0.91, 0.75, and 0.75) were recorded in 'Cheongdo-Bansi' for the calibration and prediction sets, respectively. Additionally, the acquired data were divided into two sets in a 3:1 ratio to develop predictive models and to validate the models in multiple regressions. PLSR models were developed in multiple regression to estimate the tannin content of both cultivars from firmness and simple sugars with R 2 -values of 0.83 and 0.79 in 'Cheongdo-Bansi' for the calibration and prediction sets, respectively, whereas, R 2 -values of 0.80 and 0.84 were recorded in 'Daebong' for the calibration and prediction sets, respectively. The overall findings of this study showed the possibility of using VNIR spectra for the prediction of postharvest quality and tannin contents from intact persimmon fruit with quick, chemical-free, and low-cost assessment methods. Also, the multiple regression using physicochemical parameters could fairly predict the tannin content in persimmon fruit though destructively but save time and low-cost., Competing Interests: Author IH is employed by Frusen Co., LTD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Baek, Choi, Hwang, Tilahun and Jeong.)

Chronic diseases often lead to metabolic disorders, causing anabolic resistance and increased energy consumption, which result in cachexia. Cachexia, in turn, can lead to major clinical consequences such as impaired quality of life, shortened life expectancy, and increased healthcare expenditure. Existing international diagnostic criteria for cachexia employ thresholds derived from Western populations, which may not apply to Asians due to differing body compositions. To address this issue, the Asian Working Group for Cachexia (AWGC) was initiated. The AWGC comprises experts in cachexia research and clinical practice from various Asian countries and aims to develop a consensus on diagnostic criteria and significant clinical outcomes for cachexia in Asia. The AWGC, composed of experts in cachexia research and clinical practice from several Asian countries, undertook three-round Delphi surveys and five meetings to reach a consensus. Discussions were held on etiological diseases, essential diagnostic items for cachexia, including subjective and objective symptoms and biomarkers, and significant clinical outcomes. The consensus highlighted the importance of multiple diagnostic factors for cachexia, including chronic diseases, either or both weight loss or low body mass index, and at least one of the following: anorexia, decreased grip strength (<28 kg in men and <18 kg in women), or elevated C-reactive protein levels (>5 mg/L [0.5 mg/dL]). The AWGC proposed a significant weight change of 2% or more over a 3-6 month period and suggested a tentative cut-off value of 21 kg/m 2 for low body mass index in diagnosing cachexia. Critical clinical outcomes were determined to be mortality, quality of life as assessed by tools such as EQ-5D or the Functional Assessment of Anorexia/Cachexia Therapy, and functional status as measured by the Clinical Frailty Scale or Barthel Index, with significant emphasis on patient-reported outcomes. The AWGC consensus offers a comprehensive definition and user-friendly diagnostic criteria for cachexia, tailored specifically for Asian populations. This consensus is set to stimulate future research and enhance the multidisciplinary approach to managing cachexia. With plans to develop further guidelines for the optimal treatment, prevention, and care of cachexia in Asians, the AWGC criteria are expected to drive research across chronic co-morbidities and cancer in Asia, leading to future refinement of diagnostic criteria., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Purpose: Sarcopenia is a poor prognostic factor in cancer patients, and exercise is one of the treatments to improve sarcopenia. However, there is currently insufficient evidence on whether exercise can improve sarcopenia in patients with advanced cancers. This study examined the feasibility of exercise in advanced gastrointestinal (GI) cancer patients treated with palliative chemotherapy., Methods: Between 2020 and 2021, 30 patients were enrolled in a resistance and aerobic exercise program for six weeks. The exercise intervention program (EIP) consisted of low, moderate, and high intensity levels. Patients were asked to select the intensity level according to their ability. The primary endpoint was the feasibility of the EIP measured by compliance during the six weeks. A compliance of over 50% was considered acceptable. The secondary endpoints were changes in weight and muscle mass, safety, quality of life (QoL) and overall survival (OS)., Results: The median age of the study's participants was 60 (30-77). The total compliance to the EIP was 63.3% (19/30 patients). Sixteen (53.3%) patients had a compliance of over 80%. The attrition rate was 30.0% (9/30). The mean exercise time was 41.4 min, and the aerobic exercise was 92.3% and the resistant exercise was 73.7%, and both exercise was 66.5%. Most patients performed the moderate intensity level exercises at home or near their home. The mean skeletal muscle index (SMI) was 43.5 cm 2 /m 2 pre-chemotherapy and 42.2 cm 2 /m 2 after six weeks of chemotherapy, with a decrease of -1.2 ± 2.8 cm 2 /m 2 (-3.0%) (p = 0.030). In the poor compliance group, the mean SMI decrease was -2.8 ± 3.0 cm 2 /m 2 which was significantly different (p = 0.033); however, in the good compliance group, the mean SMI decrease was -0.5 ± 2.5 cm 2 /m 2 which was maintained over the six weeks (p = 0.337). The good compliance group had a significantly longer median OS compared with the poor compliance group (25.3 months vs. 7.9 months, HR = 0.306, 95% CI = 0.120-0.784, p = 0.014). The QoL showed a better score for insomnia (p = 0.042). There were no serious adverse events., Conclusions: The EIP during palliative chemotherapy in advanced GI cancer patients showed good compliance. In the good compliance group, muscle mass and physical functions were maintained for six weeks. The EIP was safe, and the QoL was maintained. Based on this study, further research in exercise intervention in advanced cancer patients is needed., Clinical Trial Registration: The clinical trial registration number is KCT 0005615 (CRIS, https://cris.nih.go.kr/cris/en/ ); registration date, 23rd Nov 2020., (© 2023. The Author(s).)

Purpose: This study aimed to investigate the relationship between DNA damage response (DDR)-related protein expression and the clinical outcomes of patients with gastric cancer stage IV and recurrent advanced gastric cancer patients after gastrectomy treated with palliative first-line chemotherapy. Materials and Methods: A total of 611 gastric cancer patients underwent D2 radical gastrectomy at Chung-Ang University Hospital between January 2005 and December 2017, of which 72 patients who received gastrectomy treatment with palliative chemotherapy were enrolled in this study. We performed the immunohistochemical assessment of MutL Homolog 1 (MLH1), MutS Homolog 2 (MSH2), at-rich interaction domain 1 (ARID1A), poly adenosine diphosphate-ribose polymerase 1 (PARP-1), breast cancer susceptibility gene 1 (BRCA1), and ataxia-telangiectasia mutated (ATM) using formalin-fixed paraffin-embedded samples. In addition, Kaplan-Meier survival analysis and Cox regression models were used to evaluate independent predictors of overall survival (OS) and progression-free survival (PFS). Results: Among the 72 patients studied, immunohistochemical staining analysis indicated deficient DNA mismatch repair (dMMR) in 19.4% of patients (n = 14). The most common DDR gene with suppressed expression was PARP-1 (n = 41, 56.9%), followed by ATM (n = 26, 36.1%), ARID1A (n = 10, 13.9%), MLH1 (n = 12, 16.7%), BRCA1 (n = 11, 15.3%), and MSH2 (n = 3, 4.2%). HER2 (n = 6, 8.3%) and PD-L1 (n = 3, 4.2%) were expressed in 72 patients. The dMMR group exhibited a significantly longer median OS than the MMR proficient (pMMR) group (19.9 months vs. 11.0 months; hazard ratio [HR] 0.474, 95% confidence interval [CI] = 0.239-0.937, P = 0.032). The dMMR group exhibited a significantly longer median PFS than the pMMR group (7.0 months vs. 5.1 months; HR= 0.498, 95% CI = 0.267-0.928, P = 0.028). Conclusions: Of stage IV gastric cancer and recurrent gastric cancer patients who underwent gastrectomy, the dMMR group had a better survival rate than the pMMR group. Although dMMR is a predictive factor for immunotherapy in advanced gastric cancer, further studies are needed to determine whether it is a prognostic factor for gastric cancer patients treated with palliative cytotoxic chemotherapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Purpose: This regulatory post-marketing surveillance (PMS) study was performed to evaluate the safety and effectiveness of regorafenib on Korean patients with colorectal cancer (CRC), gastrointestinal stromal tumors (GIST), and hepatocellular carcinoma (HCC) in a real-world clinical setting. Methods: This PMS was conducted as a multi-center, prospective, observational study at 34 centers in Korea from August 2013 to August 2019. The primary objective was to evaluate the safety of regorafenib in real-world practice, with the secondary objective to investigate its effectiveness, including its overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: In total, 301 patients were included in the analysis (254 patients with CRC, 14 patients with GIST, and 33 patients with HCC). The incidence rates of adverse events (AEs) were 85.0%, 78.6%, and 81.8% in patients with CRC, GIST, and HCC, respectively. The most frequent AE related to regorafenib in the three cancer types was palmar-plantar erythrodysesthesia syndrome (PPES). The ORRs of patients with CRC, GIST, and HCC were 4.7%, 0%, and 41.4%, respectively. The median PFS and OS were 2.1 and 6.1 months for CRC, respectively; 9.2 and 16.4 months for GIST, respectively; and 5.5 months and not estimated (NE) for HCC, respectively. Patients who experienced a dose modification or discontinuation of regorafenib showed significantly shorter median PFS and OS (2.2 vs. 2.6 months, respectively, P = 0.0335 for PFS; 5.3 vs. 8.5 months, respectively, P = 0.0010 for OS). Conclusion: This PMS study, which is the largest surveillance study of CRC in Korea, found no newly identified safety concerns for patients who received regorafenib in the real-world setting. Additionally, the results of this study were consisted with those previously reported in phase III trials., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Introduction: There is an increased demand for services for hospitalised older patients with acute medical conditions due to rapidly ageing population. The COMPrehensive geriatric AsseSSment and multidisciplinary team intervention for hospitalised older adults (COMPASS) study will test the effectiveness of comprehensive geriatric assessment (CGA) and multidisciplinary intervention by comparing it with conventional care among acute hospitalised older adults in Korea., Methods and Analysis: A multicentre trial within a cohort comprising three substudies (randomised controlled trials) will be conducted. The intervention includes CGA and CGA-based multidisciplinary interventions by physicians (geriatricians, oncologists), nurses, nutritionists and pharmacists. The multidisciplinary intervention includes nutritional support, medication review and adjustment, rehabilitation, early discharge planning and prevention of geriatric syndromes (falls, delirium, pressure sore and urinary retention). The analysis will be based on an intention-to-treat principle. The primary outcome is living at home 3 months after discharge. In addition to assessing the economic effects of the intervention, a cost-utility analysis will be conducted., Ethics and Dissemination: The study protocol was reviewed and approved by the ethics committees of Seoul National University Bundang Hospital and each study site. The study findings will be published in peer-reviewed journals. Subgroup and further in-depth analyses will subsequently be published., Trial Registration Number: KCT0006270., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Population-based analyses of the treatment outcomes of colorectal cancer (CRC) in Asian countries are limited. Therefore, we conducted a nationwide study to assess the relationship between the timing and duration of adjuvant chemotherapy (AC) and survival in patients with CRC in South Korea. Methods: Data on AC from the Health Insurance Review and Assessment Service Database (HIRA) were analyzed, and the survival of patients who underwent curative-intent surgical resection for CRC between 2011 and 2014 was investigated. Results: From the HIRA data, 45,992 patients with stage II-III CRC were identified. Chemotherapy regimens were administered as follows: 10,640 (23.3%) received 5-fluorouracil and leucovorin/capecitabine (FL/CAP), 13,083 (28.7%) received FL/CAP plus oxaliplatin (FOLFOX/CAPOX), 299 (0.7%) received uracil and tegafur/doxifluridine (UFT/D), and 21,570 (47.3%) underwent surgery alone. Patients who did not receive AC had worse survival than those who received AC in both the colon and rectum groups (HR, 1.96, 95% CI, 1.85-2.07 and HR, 2.18, 95% CI, 2.01-2.37, respectively). Regarding patients with stage II-III CRC, AC initiation ≥ 2 months after surgery was associated with a significant decrease in overall survival (OS) (FL/CAP: HR, 1.82; 95% CI, 1.53-2.17 and FOLFOX/CAPOX: HR, 2.92; 95% CI, 2.47-3.45); however, the effects of UFT/D regimens were not statistically significant. For patients with stage II-III colon cancer, AC <3 months had lower OS (FL/CAP: HR, 3.72, 95% CI, 2.80-4.94; FOLFOX/CAPOX: HR, 2.15, 95% CI, 1.87-2.47; and UFT/D: HR, 1.74, 95% CI, 0.56-5.41). In terms of patients with stage II-III rectal cancer, AC <3 months, regardless of chemotherapy regimens, had a significant lower survival (FL/CAP: HR, 1.91, 95% CI, 1.66-2.20; FOLFOX/CAPOX: HR, 2.20, 95% CI, 1.75-2.77; and UFT/D: HR, 3.71, 95% CI, 1.45-9.44). Conclusions : Postoperative time to initiation and duration of AC were associated with survival. Based on our results, initiating AC within 2 months after surgery and administering AC for >3 months can potentially have an OS benefit in patients with stage II-III CRC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: GV1001 is a human telomerase peptide vaccine that induces a CD4/CD8 T-cell response against cancer cells, thereby affording an immunological anti-tumor effect. Here, we evaluated the efficacy and safety of GV1001 in combination with chemotherapy in patients with metastatic colorectal cancer who had failed first-line chemotherapy. Methods: This multicenter, non-randomized, single-arm phase II study recruited recurrent or metastatic colorectal cancer patients with measurable disease who had failed first-line chemotherapy. Patients received GV1001 and chemotherapy concomitantly based on a pre-established schedule. Cytotoxic chemotherapy and targeted agents (bevacizumab, cetuximab, or aflibercept) were allowed to be used at the discretion of the investigator. The primary endpoint was the disease control rate; secondary endpoints were the objective response rate, progression-free survival, overall survival, and safety outcomes. The baseline serum eotaxin level (a potential predictive biomarker of GV1001) was analyzed. To determine whether an adequate immune response had been induced, a delayed-type hypersensitivity test and a T-cell proliferation test were performed. Results: From May 13, 2015 to October 13, 2020, 56 patients with recurrent or metastatic colorectal cancer treated in seven hospitals of South Korea were enrolled. The median patient age was 64 years (range, 29-82 years); 67.9% were men. Of all patients, 66.1% had left-side colorectal cancer and the RAS mutation was present in 25%. The disease control rate and the objective response rates were 90.9% (95% confidence interval [CI]: 82.4-99.4%) and 34.1% (95% CI, 20.1-48.1%), respectively. The median progression-free survival was 7.1 months (95% CI, 5.2-9.1 months) and the median overall survival was 12.8 months (95% CI, 9.9-15.8 months). The most common all-grade adverse events were neutropenia (48.2%), nausea (26.8%), neuropathy (25.0%), stomatitis (21.4%), and diarrhea (21.4%). Immune response analysis showed that no patient had positive delayed-type hypersensitivity test results; antigen-specific T-cell proliferation was observed in only 28% of patients. The baseline eotaxin level was not associated with any efficacy outcome. Conclusion: Although no clear GV1001-specific immune response was observed, the addition of GV1001 vaccination to chemotherapy was tolerable and associated with modest efficacy outcomes., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Purpose: This study aimed to investigate the relationship between DNA damage response (DDR) related protein expression and clinical outcomes of patients with stage II and III gastric cancer undergoing gastrectomy. Materials and Methods: From January 2005 to December 2017, 217 gastrectomized patients with stage II and III gastric cancer were analyzed for disease-free and overall survival (DFS and OS, respectively) based on their DDR expression status. We performed the immunohistochemical assessment of MLH1, MSH2, at-rich interaction domain 1 (ARID1A), poly adenosine diphosphate-ribose polymerase 1 (PARP-1), breast cancer susceptibility gene 1 (BRCA1), and ataxia-telangiectasia mutated (ATM) using formalin-fixed paraffin-embedded (FFPE) samples. Results : Among the 217 patients studied, the most common DDR gene whose expression was suppressed was high PARP-1 (n = 120, 55.3%), followed by ATM (n = 62, 28.6%), ARID1A (n = 45, 20.7%), MLH1 (n = 33, 15.2%), BRCA1 (n = 25, 11.5%), and MSH2 (n = 9, 4.1%). The low-expression PARP-1 group exhibited a significantly shorter 5-year OS rate than the high-expression PARP-1 group (48.1% vs. 62.7%; HR 1.519, 95% CI = 1.011-2.283, P = 0.044). In the multivariate OS analysis, TNM stage (II vs. III) (HR = 5.172, P < 0.001), low PARP-1 expression (HR = 1.697, P = 0.013) and adjuvant chemotherapy (HR = 0.382, P < 0.001) were the only significant prognostic factors. Conclusions : Low PARP-1 expression level could be an indicator of poor prognosis in gastrectomized patients with stage II and III gastric cancer., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: The efficacy of modified FOLFIRINOX (mFOLFIRINOX) as a second-line chemotherapy treatment for metastatic pancreatic adenocarcinoma (mPAC), remains unclear. This multi-center randomised phase III trial aimed to elucidate the efficacy of mFOLFIRINOX as a second-line chemotherapy treatment for mPAC patients with good performance status., Patients and Methods: Eighty mPAC patients (age, 19-75 years) refractory to first-line gemcitabine-based chemotherapy were randomly selected to receive mFOLFIRINOX or S-1. mFOLFIRINOX comprised oxaliplatin (65 mg/m 2 ), irinotecan (135 mg/m 2 ), and leucovorin (400 mg/m 2 ) on day 1 and continuous 5-FU infusion (1000 mg/m 2 ) over 24 h on days 1-2 every 2 weeks. S-1 comprised body surface area-dependent oral S-1, divided into two doses per day on days 1-28 every 6 weeks., Results: Overall survival was the primary endpoint. The objective response and disease control rates were higher in the mFOLFIRINOX than in the S-1 group (15% versus 2%; p = .04 and 67% versus 37%; p = .007). The median progression-free survival rates were 5.2 and 2.2 months in the mFOLFIRINOX and S-1 groups, respectively (adjusted hazard ratio [HR]: .4; 95% confidence interval [CI]: .2-.6; p < .001). The median overall survival rates were 9.2 and 4.9 months in the mFOLFIRINOX and S-1 groups, respectively (adjusted HR: .4; 95% CI: .2-.7; p = .002). Grade 3-4 adverse events occurred in 56% and 17% of the patients in the mFOLFIRINOX and S-1 groups, respectively (p < .001)., Conclusion: Administration of mFOLFIRINOX as a second-line chemotherapy treatment for mPAC patients refractory to gemcitabine-based chemotherapy resulted in increased survival rates than S-1 treatment alone., Competing Interests: Conflict of interest statement The authors have declared no conflict of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Salvia plebeia has been used to treat a variety of inflammatory diseases, as well as colds and bronchitis. Macrophages have antioxidant defense mechanisms to cope with the intracellular reactive oxygen species (ROS) produced as part of the immune response. The nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase (HO)-1 pathway in inflamed macrophages is an appealing target due to its protective effect against ROS-induced cell damage. In this study, nepetoidin B (NeB) was first isolated from S. plebeia and identified by nuclear magnetic resonance spectroscopy. NeB reduced pro-inflammatory mediators (nitric oxide and prostaglandin E 2 ) and cytokines (tumor necrosis factor-α, interleukin (IL)-6, and IL-1β) in LPS-activated RAW 264.7 cells by inhibiting the NF-κB signaling pathway. In the NeB-treated group, catalase and superoxide dismutase levels were significantly higher, and ROS expression decreased. By activating Nrf2 signaling, NeB enhanced HO-1 expression. Furthermore, when the cells were pretreated with tin protoporphyrin (an HO-1 inhibitor), the anti-inflammatory effects of NeB were reduced. Therefore, NeB may activate the Nrf2/ HO-1 pathway. These results reveal the NeB isolated from S. plebeia exerts anti-inflammatory effects by modulating NF-κB signaling and activating the Nrf2/HO-1 pathway in LPS-stimulated RAW 264.7 cells.

Purpose: This study was conducted to determine the effectiveness of immune checkpoint inhibitors (ICIs) in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) after platinum-containing chemotherapy. We also identified clinical biomarkers which may be predictive of patient prognosis., Materials and Methods: We analyzed 125 patients with R/M HNSCC who received ICIs, retrospectively. Overall response rate (ORR) was the primary study outcome. Overall survival (OS) and progression-free survival (PFS) were the secondary study outcomes., Results: The patients received anti-programmed cell death protein-1 (PD-1) (n=73, 58%), anti-programmed death-ligand 1 (PD-L1) (n=24, 19%), or a combination of anti-PD-1/PD-L1 and anti-cytotoxic T-lymphocyte antigen 4 (n=28, 22%). The median age was 57 years (range, 37 to 87). The location of the primary tumor was in the oral cavity in 28% of the cases, followed by oropharynx (27%), hypopharynx (20%), and larynx (12%). The ORR was 15% (19/125). With 12.3 months of median follow-up, median PFS was 2.7 months. Median OS was 10.8 months. A neutrophil-to-lymphocyte ratio (NLR) > 4 was significantly associated with poor response to ICIs (odds ratio, 0.30; p=0.022). A sum of the target lesions > 40 mm (hazard ratio [HR], 1.53; p=0.046] and a NLR > 4 (HR, 1.75; p=0.009) were considered to be predictive markers of short PFS. A poor performance status (HR, 4.79; p < 0.001), a sum of target lesions > 40 mm (HR, 1.93; p=0.025), and an NLR > 4 (HR, 3.36; p < 0.001) were the significant predictors for poor survival., Conclusion: ICIs exhibited favorable antitumor activity in R/M HNSCC. Clinically, our findings can be used to recognize patients benefit from receiving ICI.

Background/aims: This nationwide study was undertaken to determine differences in clinicopathologic characteristics and survival of patients with colorectal cancer (CRC) according to age using big data from the Korean National Health Insurance Service (NHIS)., Methods: The NHIS data including quality assessment of CRC by the Health Insurance Review & Assessment Service in Korea between 2011 and 2014 were analyzed. Based on age, patients were divided into three groups: not-old patients (< 65), young-old patients (65 to 74 years old) and old-old patients (≥ 75 years old)., Results: We included 71,513 CRC patients. The median follow-up duration was 3.2 years (range, 0.003 to 5.5). Male patients constituted 60%. The median age of patients was 65 years (range, 18 to 102). Colon was the cancer site in 59.8% of not-old patients, 62.9% of young-old patients, and 66.1% of old-old patients. Compared to not-old patients, young-old and old-old patients were more likely to be diagnosed with colon adenocarcinoma and well/moderate differentiation or adequate differentiation (all p < 0.001). Old patients underwent more emergency operation (p < 0.001) and received less adjuvant therapy in stage I-III (p < 0.001). The probability of 3-year survival of young-old or old-old patients was worse than that for not-old patients (hazard ratio [HR], 1.55; 95% confidence interval [CI], 1.46 to 1.64) (HR, 3.19; 95% CI, 3.03 to 3.37)., Conclusion: Old patients with CRC show different histology from younger patients. They are more frequently to have colon as primary lesion. They undergo less adjuvant therapy. Further studies and evidence-based guidelines for older patients with CRC are warranted to improve their outcome.

Background: Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC., Patients and Methods: The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m 2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146)., Results: A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable., Conclusions: In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy., Competing Interests: Disclosure The authors have declared no conflicts of interest. Data sharing Data generated and analyzed during this study are on file at the Samsung Medical Center, and are not publicly available. Data can be shared upon request., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Many studies have analyzed the effects of β -cryptoxanthin (BCX) on osteoporosis and bone health. This systematic review and meta-analysis aimed at providing quantitative evidence for the effects of BCX on osteoporosis. Publications were selected and retrieved from three databases and carefully screened to evaluate their eligibility. Data from the final 15 eligible studies were extracted and uniformly summarized. Among the 15 studies, seven including 100,496 individuals provided information for the meta-analysis. A random effects model was applied to integrate the odds ratio (OR) to compare the risk of osteoporosis and osteoporosis-related complications between the groups with high and low intake of BCX. A high intake of BCX was significantly correlated with a reduced risk of osteoporosis (OR = 0.79, 95% confidence interval (CI) 0.70-0.90, p = 0.0002). The results remained significant when patients were stratified into male and female subgroups as well as Western and Asian cohorts. A high intake of BCX was also negatively associated with the incidence of hip fracture (OR = 0.71, 95% CI 0.54-0.94, p = 0.02). The results indicate that BCX intake potentially reduces the risk of osteoporosis and hip fracture. Further longitudinal studies are needed to validate the causality of current findings.

Old age alone does not reflect an intolerability to chemotherapy. However, upfront dose reduction (UDR) of the first cycle of first-line palliative chemotherapy has sometimes been chosen by physicians for older adults with metastatic cancer due to concerns regarding adverse events. The development of predictive factors for UDR of palliative chemotherapy would be helpful for treatment planning among older adults. This was a secondary analysis of a study on predicting adverse events of first-line palliative chemotherapy in 296 patients (≥70 years) with solid cancer. We assessed the prevalence of UDR of the first cycle of first-line chemotherapy and the association of UDR with the variables of geriatric assessment (GA) and chemotherapy compliance. Among the 296 patients, 177 (59.8%) patients were treated with UDR. The mean percentage of UDR for the total patient group was 19.2% (range: 4-47%) of the standard dose. In a multivariate analysis, poor performance status (PS) and living without a spouse were independent predictive factors of UDR of first-line palliative chemotherapy in older adults. Patients with UDR showed fewer grade 3-5 adverse events versus the standard dose group. Study completion as planned was significantly higher in the UDR group versus the standard dose group. Older adults with UDR better tolerated chemotherapy than patients with a standard dose.

Purpose: Although immune-checkpoint inhibitors (ICIs) have emerged as therapeutic options for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M-HNSCC), concerns have been raised on exceptional acceleration of tumor growth during treatment with ICIs, a condition described as hyperprogressive disease (HPD). This study examined the incidence, potential predictors, and clinical impact of HPD in R/M-HNSCC., Methods: We retrospectively collected data of patients with R/M-HNSCC treated with ICIs between January 2013 and June 2018 from 11 medical centers in Korea. HPD was defined as tumor growth kinetics ratio (TGKr) > 2, which was calculated by comparing TGK on ICIs with that before treatment with ICIs., Results: Of 125 patients, 68 (54.4%) obtained progressive disease as their best responses (progressors). HPD was identified in 18 (26.5% of progressors, 14.4% of total) patients. Relatively younger age, primary tumor of oral cavity, and previous locoregional irradiation were significant predictors of HPD according to multivariable analysis (p = 0.040, 0.027, and 0.015, respectively). Compared to patients without HPD, patients with HPD had significantly shorter median progression-free survival (PFS) (1.2 vs. 3.4 months, p < 0.001) and overall survival (OS) (3.4 vs. 10.7 months, p = 0.047). However, interestingly, HPD did not significantly affect the therapeutic benefit of post-ICIs chemotherapy., Conclusions: Younger patients with oral cavity cancer or prior treatment with locoregional radiotherapy could be regarded potential risk groups for HPD in patients with R/M-HNSCC treated with ICIs. Although HPD could consistently predict poorer survival outcomes, patients who experienced HPD with ICIs should not be excluded from the subsequent salvage chemotherapy treatments.

Cancer causes muscle mass loss, which is associated with a poor prognosis. Chemotherapy may also reduce muscle mass. We investigated skeletal muscle mass change during palliative chemotherapy for advanced gastric cancer (AGC) and its association with treatment outcomes. We retrospectively reviewed 111 consecutive AGC patients who underwent first-line palliative chemotherapy. Skeletal muscle area was measured before and after chemotherapy at the third lumbar vertebra level using computed tomography scans. We compared skeletal muscle index (SMI), body mass index (BMI), and body weight changes to chemotherapy response and survival. The 80 male and 31 female patients' median age was 65 (range 31-87) years, and 46.8% had sarcopenia at baseline. Median pre-chemotherapy to post-chemotherapy SMI, BMI, and body weight decreases were - 4.5 cm 2 /m 2 (- 11.3%) (P < 0.001); - 0.7 kg/m 2 (- 3.2%) (P < 0.001); and - 2.0 kg (- 3.5%) (P < 0.001), respectively. Median SMI decreases for patients with objective response, stable disease, and disease progression were - 4.0 cm 2 /m 2 (range - 20.1 ~ 9.5); - 4.5 cm 2 /m 2 (range - 19.8 ~ 0.8); and - 3.8 cm 2 /m 2 (range: - 17.6 ~ 0.1), respectively. Response to chemotherapy was not associated with SMI decrease (P = 0.463). In multivariable analysis, sarcopenia at baseline (HR 1.681; 95% CI 1.083-2.609, P = 0.021), decreased SMI (HR 1.620; 95% CI 1.041-2.520; P = 0.032) were significant poor prognostic factors for survival. Skeletal muscle mass decreased significantly during chemotherapy in AGC patients, but was not associated with chemotherapy response. Decreased SMI was a poor prognostic factor in AGC patients during first-line palliative chemotherapy.

Immune system dysfunction is associated with head and neck squamous cell carcinoma (HNSCC) development and progression and immune checkpoint inhibitors have demonstrated substantial survival benefits in platinum-refractory HNSCC; therefore, we examined the prognostic value of immune-related gene (IRG) expression in HNSCC. We analyzed the expression of 82 IRGs in 71 patients with HNSCC enrolled in a feasibility study for a prospective HNSCC biomarker-driven umbrella trial (Korean Cancer Study Group TRIUMPH study, NCT03292250). CD200R1 was identified as an independent prognostic factor and validated in GEO and TCGA database. CD2000R1 mRNA expression was found to be an independent favorable prognostic factor in patients with HNSCC. Moreover, CD200R1 was found to affect genes and pathways associated with the immune response, while seven differentially expressed genes ( CD8A, DOK2, CX3CR1, TYROBP, CXCL9, CD300LF, IFNG ) were associated with CD200R1 expression. Samples with higher CD200R1 expression displayed higher tumor-infiltrating immune cell counts both in silico and in histological analysis. These findings will help in the development of more accurate prognostic tools and suggest CD200R1 modulation as a HNSCC immunotherapy.

Background: Polypharmacy is an important issue in the care of older patients with cancer, as it increases the risk of unfavorable outcomes. We estimated the prevalence of polypharmacy, potentially inappropriate medication (PIM) use, and drug-drug interactions (DDIs) in older patients with cancer in Korea and their associations with clinical outcomes., Subjects, Materials, and Methods: This was a secondary analysis of a prospective observational study of geriatric patients with cancer undergoing first-line palliative chemotherapy. Eligible patients were older adults (≥70 years) with histologically diagnosed solid cancer who were candidates for first-line palliative chemotherapy. All patients enrolled in this study received a geriatric assessment (GA) at baseline. We reviewed the daily medications taken by patients at the time of GA before starting chemotherapy. PIMs were assessed according to the 2015 Beers criteria, and DDIs were assessed by a clinical pharmacist using Lexi-comp Drug Interactions. We evaluated the association between polypharmacy and clinical outcomes including treatment-related toxicity, and hospitalization using logistic regression and Cox regression analyses., Results: In total, 301 patients (median age 75 years; range, 70-93) were enrolled; the most common cancer types were colorectal cancer (28.9%) and lung cancer (24.6%). Mean number of daily medications was 4.7 (±3.1; range, 0-14). The prevalence of polypharmacy (≥5 medications) was 45.2% and that of excessive polypharmacy (≥10 medications) was 8.6%. PIM use was detected in 137 (45.5%) patients. Clinically significant DDIs were detected in 92 (30.6%) patients. Polypharmacy was significantly associated with hospitalization or emergency room (ER) visits (odds ratio: 1.73 [1.18-2.55], p < .01). Neither polypharmacy nor PIM use showed association with treatment-related toxicity., Conclusion: Polypharmacy, PIM use, and potential major DDIs were prevalent in Korean geriatric patients with cancer. Polypharmacy was associated with a higher risk of hospitalization or ER visits during the chemotherapy period., Implications for Practice: This study, which included 301 older Korean patients with cancer, highlights the increased prevalence of polypharmacy in this population planning to receive palliative chemotherapy. The prevalence of polypharmacy and excessive polypharmacy was 45.2% and 8.6%, respectively. The prescription of potentially inappropriate medications (PIMs) was detected in 45.5% and clinically significant drug-drug interaction in 30.6% of patients. Given the association of polypharmacy with increased hospitalization or emergency room visits, this study points to the need for increased awareness and intervention to minimize polypharmacy in the geriatric cancer population undergoing chemotherapy. Moreover, specific criteria for establishing PIMs should be adopted for the treatment of older adults with cancer., (© AlphaMed Press 2019.)

Background: The efficacy of epidermal growth factor (EGF) receptor (EGFR) inhibitors in patients with non-small cell lung cancer (NSCLC), pancreatic cancer (PC), or colorectal cancer (CRC) has been demonstrated. However, dermatological reactions to these inhibitors can cause significant physical and psychosocial discomfort. The objective of the present study was to evaluate the efficacy of EGF ointment for EGFR inhibitor-related skin adverse events (ERSEs)., Materials and Methods: This placebo-controlled, double-blind, multicenter, pilot phase III trial enrolled patients with NSCLC, PC, or CRC treated with EGFR inhibitors. Patients with grade ≥2 ERSEs were included. Patients were randomized to three treatment arms: arm 1, placebo; arm 2, 1 ppm of EGF ointment; and arm 3, 20 ppm of EGF ointment. Patients applied ointment to their skin lesions twice daily., Results: Efficacy evaluation was available for 80 patients (9 for PC, 28 for NSCLC, and 43 for CRC). Responses were 44.4% in arm 1, 61.5% in arm 2, and 77.8% in arm 3. There was a linear correlation between EGF concentrations and responses (p = .012). Quality of life (QoL) was assessed for 74 patients. Maximum changes in composite scores by Skindex-16 after treatment were significantly different among arms (mean ± SD: -5.2 ± 8.6 for arm 1, -11.7 ± 14.2 for arm 2, and - 18.6 ± 17.7 for arm 3; p = .008). EGF arms showed significant improvement in emotions (p = .005) and functioning (p = .044) scores over the placebo arm., Conclusion: EGF ointment is effective for managing ERSEs. It can also improve patients' QoL compared with placebo. Clinical trial identification number. NCT02284139 IMPLICATIONS FOR PRACTICE: Patients with non-small cell lung cancer, pancreatic cancer, or colorectal cancer who are treated with epidermal growth factor (EGF) receptor (EGFR) inhibitors may experience dermatologic reactions to their treatment. This study investigated the benefit of an EGF ointment in the treatment of these adverse events and observed the ointment to be effective in managing EGFR inhibitor-related skin adverse events., (© 2019 The Authors. The Oncologist published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

The balloon flower (BF) is a potent natural source of phytochemical compounds and is associated with our health. The sprouting process is accompanied by significant changes in phytochemical compounds in comparison with their original plants. Even though many studies are conducted with BF, there are not yet reports of BF sprouts. In the present study, we determined the chemical composition and biological activity of BF sprouts that had been cultivated for 50 days. Kaempferol-3-O-galactoside and 1-O-caffeoylquinic acid were identified as major components of whole BF sprouts. The leaves/stems of the sprouts had higher total phenolic and flavonoid contents and lower IC 50 values in DPPH • and ABTS •+ scavenging assays than whole sprouts or roots. The roots of the sprouts had the highest polygalacin D content (1.44 mg/g). We also determined the effects of different parts of BF sprouts on RAW 264.7 macrophage cells. When these cells were stimulated with lipopolysaccharide (LPS), their nitrite and pro-inflammatory cytokine production increased. BF sprouts suppressed the LPS-induced production of nitrite, tumor necrosis factor-α, and interleukin-6 in a concentration-dependent manner without causing any cytotoxic effects. Nitrite and pro-inflammatory cytokine production were significantly inhibited by the roots and leaves/stems, respectively. The inhibitory effects of BF sprouts on LPS-stimulated inflammatory responses in RAW 264.7 macrophage cells were associated with suppressed NF-κB activation. These findings suggest that BF sprouts could be a valuable source of bioactive compounds and exert anti-inflammatory effects due to their polygalacin D, deapi-platycodin D 3, and polyphenol content., Competing Interests: The authors declare no conflict of interest., (© 2019 The Authors. Food Science & Nutrition published by Wiley Periodicals, Inc.)

Even after extensive standard evaluation, the probable cause of stroke in some patients remains unclear; this condition is defined as cryptogenic stroke (CS). The prognosis of patients with CS is largely undetermined. We investigated whether higher brachial-ankle pulse wave velocities (baPWVs) can predict poor functional outcomes at 3 months after stroke onset in these patients. We investigated patients with CS with first-ever acute cerebral infarction who underwent baPWV measurements. The stroke subtypes were classified using the Trial of ORG 10172 in Acute Stroke Treatment classification. Poor functional outcomes were defined as modified Rankin Scale scores of >2 at 3 months after stroke onset. In total, 595 patients with CS were included; among them, 360 were men (60.5%). Their mean age was 65.0 ± 12.4 years. One-hundred-eleven patients (18.7%) had poor functional outcomes. In the multivariable logistic regression analysis, the cutoff baPWV value based on the receiver-operating characteristic curve was >1968 cm/s, which was determined as a strong independent predictor (OR 3.159, 95% CI 1.487-6.715, p = 0.003). The OR of the cutoff value was higher in the patients with CS with initial National Institutes of Health Stroke Scale (NIHSS) scores of ≥5 (OR 4.252, 95% CI 1.596-11.324, p = 0.004); that in the patients with initial NIHSS scores of <5 was not significant (OR 1.671, 95% CI 0.620-4.505, p = 0.310). baPWV measurement during the acute stroke phase might be useful in identifying patients with CS at high risks of having a poor neurological prognosis., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objectives: We aimed to explore serum biomarkers for predicting survival of older patients with metastatic solid tumors who received first line palliative chemotherapy., Materials and Methods: Serum samples were prospectively collected before first-line chemotherapy at 11 academic centers in Korea. All patients were participants in a prospective cohort study of older patients with metastatic solid tumors. Serum levels of C-reactive protein (CRP), CXCL10, SIRT1, VEGF-A, activin A, C-terminal telopeptide of type I collagen (CTx), total 25-hydroxyvitamin D were measured by ELISA and interleukin-6 (IL-6), myostatin, irisin, FGF-19, FGF-21, FGF-23 by Luminex multiplex assay. Overall survival (OS) was determined., Results: Serum samples from 138 patients (median age: 75 years, range: 70-92 years) were collected from February 2014 to December 2016. During a median follow up time of 13.8 months, 73 (52.9%) patients died. Among 13 serum markers, CRP (log-rank, P = 0.009), activin A (P = 0.007), and myostatin (P = 0.047) were significantly correlated with OS in univariate analyses. Activin A (hazard ratio [HR] 2.22, 95% confidence interval [CI] 1.32-3.72; P = 0.003) and myostatin (HR 3.02, 95% CI 1.39-6.57; P = 0.005) were significantly associated with OS after adjustment for other clinical factors. In predicting early (6-month) mortality, two inflammatory markers, IL-6 and CRP, were included in the decision-tree model., Conclusion: In older patients with cancer, high serum concentrations of activin A and myostatin were predictive of poor OS. IL-6 and CRP might be useful to select older patients at risk of early mortality. These markers could be incorporated into predictive tools for clinical decision-making and warrant further investigation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

We developed low temperature-aged garlic (LTAG) to remove its unique and spicy flavor and evaluated the anti-fatigue properties of LTAG against exercise-induced fatigue in mice. In the results, the treadmill running time to exhaustion in the mice fed LTAG was prolonged compared with the control. There was significant difference in blood parameters of glucose, lactate, lactate dehydrogenase (LDH), and free fatty acid (FFA) concentration between the LTAG-fed mice and the control. In addition, LTAG effectively increased the content of glycogen and creatine kinase and the activity of antioxidant enzymes in the muscle. The mechanism underlying the anti-fatigue activity of LTAG is hypothesized to involve increase in postexercise tissue glycogen accumulation to improve the aerobic and anaerobic exercise capacity. LTAG may have an ergogenic effect on endurance exercise while decreasing the levels of FFA, LDH, and lactate, which are associated with the anti-fatigue effect. Thus, LTAG has potential as a pharmacological anti-fatigue agent.

Purpose : Acute kidney injury (AKI) affects cancer therapy outcome and increases morbidity and mortality in cancer patients. We investigated the incidence, risk factors, and clinical outcomes of AKI caused by palliative chemotherapy in lung cancer patients. Materials and Methods : Between January 2005 and November 2014, 207 lung cancer patients who had been treated with first-line palliative chemotherapy were enrolled. Renal function was assessed during every cycle of chemotherapy. AKI was defined based on changes in serum creatinine levels as described in the Kidney Disease: Improving Global Outcomes guidelines. Clinical outcomes were evaluated depending on AKI occurrence during the first-line chemotherapy. Results : Of the 207 patients, 36 (17.4%) experienced AKI. Among the 36 patients who developed AKI during chemotherapy, 33 (91.8%) had AKI stage I. Although 19 patients (52.7%) with AKI during chemotherapy progressed to chronic kidney disease (CKD), no patients were reported to progress to end-stage renal disease (ESRD). The number of chemotherapy cycles was independently associated with chemotherapy-induced AKI in multivariate analysis (OR = 1.71, 95% CI 1.29-2.26, p < 0.001). The median follow-up duration was 83 months. Patients with AKI during chemotherapy (AKI group) showed significantly longer time to treatment failure than patients without AKI (non-AKI group) (4.2 vs. 2.5 months, p < 0.001). However, the median overall survival (11.7 vs. 8.8 months, p = 0.147) and progression-free survival (5.5 vs. 5.2 months, p = 0.347) were not different between the groups. Conclusions : AKI that developed during chemotherapy was mostly of mild degree and its prognosis was favorable. The occurrence of AKI was associated with the number of chemotherapy cycles administered. AKI did not adversely affect survival of lung cancer patients during chemotherapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Purpose: Our purpose was to assess the differences in growth rates of multiple pulmonary metastatic nodules using three-dimensional (3D) computed tomography (CT) volumetry and propose a concept of CT spatial tumor heterogeneity., Materials and Methods: We manually measured the largest diameter of metastatic pulmonary nodules on chest CT scans, and calculated the 3D maximum diameter and the volume using a semi-automated 3D CT volumetry of each nodule. The tumor response was assessed according to the revised RECIST 1.1. We defined a nodule as an outlier based on 1.5 times growth during follow-up. The CT spatial tumor heterogeneity was statistically analyzed by the "minimum combination t-test method" devised in our study., Results: On manual measurement, the tumor response category was stable disease (SD) in all 10 patients. Of them, total 155 metastatic nodules (4-52 nodules per patient) were segmented using the 3D CT volumetry. In the 3D maximum diameter, 9 patients had SD except for one patient with partial response in the two selected nodules; for the volume, all 10 patients were SD. For the 3D maximum diameter, six patients had at least one outlier; whereas five patients had the outlier on the volume measurement. Six patients were proven to have overall CT spatial tumor heterogeneity., Conclusions: The spatial tumor heterogeneity determined in a CT parametric approach could be statistically assessed. In patients with CT spatial heterogeneity, tumors with different growth rates may be neglected when the nodules are assessed according to the current guideline., Competing Interests: The authors have declared that no competing interests exist.

The histological features of thrombus in stroke patients with cancer are not well known. Using immunohistochemical staining of thrombi retrieved during mechanical thrombectomy in stroke patients, thrombus compositions were compared between 16 patients with active cancer, 16 patients with inactive cancer, and 16 patients without any history of cancer. The active cancer group showed higher platelet and lower erythrocyte fractions than the inactive cancer or the control group. Four patients with vegetation showed very high platelet and low erythrocyte fractions. Patients with cryptogenic etiology in the active cancer group showed a similar pattern to those with vegetation. These findings may aid the determination of treatment strategies in cancer-associated stroke. ANN NEUROL 2019., (© 2019 American Neurological Association.)

Purpose: The purpose of this study was to prospectively validate the Korean Cancer Study Group Geriatric Score (KG)-7, a novel geriatric screening tool, in older patients with advanced cancer planned to undergo first-line palliative chemotherapy., Materials and Methods: Participants answered the KG-7 questionnaire before undergoing geriatric assessment (GA) and first-line palliative chemotherapy. The performance of KG-7 was evaluated by calculating the sensitivity (SE), specificity (SP), positive and negative predictive value (PPV and NPV), balanced accuracy (BA), and area under the curve (AUC)., Results: The baseline GA and KG-7 results were collected from 301 patients. The median age was 75 years (range, 70 to 93 years). Abnormal GA was documented in 222 patients (73.8%). Based on the ≤ 5 cut-off value of KG-7 for abnormal GA, abnormal KG-7 score was shown in 200 patients (66.4%). KG-7 showed SE, SP, PPV, NPV, and BA of 75.7%, 59.7%, 84.4%, 46.0%, and 67.7%, respectively; AUC was 0.745 (95% confidence interval, 0.687 to 0.803). Furthermore, patients with higher KG-7 scores showed significantly longer survival (p=0.006)., Conclusion: KG-7 appears to be adequate in identifying patients with abnormal GA prospectively. Hence, KG-7 can be a useful screening tool for Asian countries with limited resources and high patient volume.

Breast cancer type 1 susceptibility protein (BRCA1) is a tumor suppressor gene that encodes a nuclear phosphoprotein, which is involved in homologous recombination to repair DNA double strand breaks and maintain genome stability. When BRCA1 is mutated or altered, DNA damage may not be effectively repaired, which leads to DNA replication errors and cancer growth. Accordingly, people carrying a mutation in the BRCA1 gene possess an increased risk of several types of cancer, including breast and ovarian cancer. Previous clinical studies have reported an association between BRCA1 expression level and the incidence of gastric cancer; however, to the best of our knowledge, an in vitro study has not been performed to support these clinical observations. Therefore, the present study evaluated BRCA1 expression levels in gastric cancer cell lines. In addition, the IC 50 values of cisplatin and oxaliplatin in each cell line were determined to investigate a potential correlation between BRCA1 expression level and chemosensitivity to platinum agents. The present results revealed that the BRCA1 expression level in gastric cancer is variable and associated with the treatment response to platinum-based chemotherapy. This suggests that BRCA1 may serve as a therapeutic marker for platinum-based chemotherapy in gastric cancer.

Background: Early-onset or familial gastric cancer (GC) is known to have clinicopathologic profiles different from those of sporadic GC. We aimed to compare DNA damage response marker expression between early-onset or familial GC and sporadic GC. Methods: GC samples were obtained from patients who underwent gastrectomy for GC at Seoul National University Hospital. Immunohistochemical analyses of various DNA damage response markers, including BRCA1, BRCA2, MRE11, RAD51C, and γH2AX, were performed using 54 early-onset GC, 59 familial GC, and 337 sporadic GC tissue microarray samples. Correlations between marker expression and clinicopathologic features were evaluated by univariate and multivariate analyses, and overall survival was analyzed. Results: The rate of γH2AX positivity was significantly higher (p < 0.001) in early-onset or familial GC than in sporadic GC. In contrast, the rates of MRE11 negativity and RAD51C negativity were significantly higher in sporadic GC than in early-onset or familial GC. BRCA1 negativity was associated with decreased overall survival in sporadic GC (p = 0.002), and MRE11 negativity was associated with decreased overall survival in sporadic GC (p = 0.012). Conclusion: Our results show significant differences in DNA damage response marker expression between early-onset or familial GC and sporadic GC., (Creative Commons Attribution License)