1.First-in-Human Phase 1 Study of a B Cell– and Monocyte-Based Immunotherapeutic Vaccine against HER2-Positive Advanced Gastric Cancer
Minkyu JUNG ; Jii Bum LEE ; Hyo Song KIM ; Woo Sun KWON ; Hyun Ok KIM ; Sinyoung KIM ; Myunghwan PARK ; Wuhyun KIM ; Ki-Young CHOI ; Taegwon OH ; Chang-Yuil KANG ; Hyun Cheol CHUNG ; Sun Young RHA
Cancer Research and Treatment 2024;56(1):208-218
Purpose:
BVAC-B is an autologous B cell– and monocyte-based immunotherapeutic vaccine that contains cells transfected with a recombinant human epidermal growth factor receptor 2 (HER2) gene and loaded with the natural killer T cell ligand alpha-galactosylceramide. Here, we report the first BVAC-B study in patients with HER2-positive advanced gastric cancer.
Materials and Methods:
Patients with advanced gastric cancer refractory to standard treatment with HER2+ immunohistochemistry ≥ 1 were eligible for treatment. Patients were administered low (2.5×107 cells/dose), medium (5.0×107 cells/dose), or high dose (1.0×108 cells/dose) of BVAC-B intravenously four times every 4 weeks. Primary endpoints included safety and maximum tolerated BVAC-B dose. Secondary endpoints included preliminary clinical efficacy and BVAC-B-induced immune responses.
Results:
Eight patients were treated with BVAC-B at low (n=1), medium (n=1), and high doses (n=6). No dose-limiting toxicity was observed, while treatment-related adverse events (TRAEs) were observed in patients treated with medium and high doses. The most common TRAEs were grade 1 (n=2) and grade 2 (n=2) fever. Out of the six patients treated with high-dose BVAC-B, three had stable disease with no response. Interferon gamma, tumor necrosis factor-α, and interleukin-6 increased after BVAC-B treatment in all patients with medium and high dose, and HER2-specific antibody was detected in some patients.
Conclusion
BVAC-B monotherapy had a safe toxicity profile with limited clinical activity; however, it activated immune cells in heavily pretreated patients with HER2-positive gastric cancer. Earlier treatment with BVAC-B and combination therapy is warranted for evaluation of clinical efficacy.
2.Early Prediction of Mortality for Septic Patients Visiting Emergency Room Based on Explainable Machine Learning: A Real-World Multicenter Study
Sang Won PARK ; Na Young YEO ; Seonguk KANG ; Taejun HA ; Tae-Hoon KIM ; DooHee LEE ; Dowon KIM ; Seheon CHOI ; Minkyu KIM ; DongHoon LEE ; DoHyeon KIM ; Woo Jin KIM ; Seung-Joon LEE ; Yeon-Jeong HEO ; Da Hye MOON ; Seon-Sook HAN ; Yoon KIM ; Hyun-Soo CHOI ; Dong Kyu OH ; Su Yeon LEE ; MiHyeon PARK ; Chae-Man LIM ; Jeongwon HEO ; On behalf of the Korean Sepsis Alliance (KSA) Investigators
Journal of Korean Medical Science 2024;39(5):e53-
Background:
Worldwide, sepsis is the leading cause of death in hospitals. If mortality rates in patients with sepsis can be predicted early, medical resources can be allocated efficiently. We constructed machine learning (ML) models to predict the mortality of patients with sepsis in a hospital emergency department.
Methods:
This study prospectively collected nationwide data from an ongoing multicenter cohort of patients with sepsis identified in the emergency department. Patients were enrolled from 19 hospitals between September 2019 and December 2020. For acquired data from 3,657 survivors and 1,455 deaths, six ML models (logistic regression, support vector machine, random forest, extreme gradient boosting [XGBoost], light gradient boosting machine, and categorical boosting [CatBoost]) were constructed using fivefold cross-validation to predict mortality. Through these models, 44 clinical variables measured on the day of admission were compared with six sequential organ failure assessment (SOFA) components (PaO 2 /FIO 2 [PF], platelets (PLT), bilirubin, cardiovascular, Glasgow Coma Scale score, and creatinine).The confidence interval (CI) was obtained by performing 10,000 repeated measurements via random sampling of the test dataset. All results were explained and interpreted using Shapley’s additive explanations (SHAP).
Results:
Of the 5,112 participants, CatBoost exhibited the highest area under the curve (AUC) of 0.800 (95% CI, 0.756–0.840) using clinical variables. Using the SOFA components for the same patient, XGBoost exhibited the highest AUC of 0.678 (95% CI, 0.626–0.730). As interpreted by SHAP, albumin, lactate, blood urea nitrogen, and international normalization ratio were determined to significantly affect the results. Additionally, PF and PLTs in the SOFA component significantly influenced the prediction results.
Conclusion
Newly established ML-based models achieved good prediction of mortality in patients with sepsis. Using several clinical variables acquired at the baseline can provide more accurate results for early predictions than using SOFA components. Additionally, the impact of each variable was identified.
3.Immunogenicity and Safety of Vaccines against Coronavirus Disease in Actively Treated Patients with Solid Tumors: A Prospective Cohort Study
Yae Jee BAEK ; Youn-Jung LEE ; So Ra PARK ; Kyoo Hyun KIM ; Seung-Hoon BEOM ; Choong-kun LEE ; Sang Joon SHIN ; Sun Young RHA ; Sinyoung KIM ; Kyoung Hwa LEE ; Jung Ho KIM ; Su Jin JEONG ; Nam Su KU ; Jun Yong CHOI ; Joon-Sup YEOM ; Minkyu JUNG ; Jin Young AHN
Cancer Research and Treatment 2023;55(3):746-757
Purpose:
We aimed to assess the humoral response to and reactogenicity of coronavirus disease 2019 (COVID-19) vaccination according to the vaccine type and to analyze factors associated with immunogenicity in actively treated solid cancer patients (CPs).
Materials and Methods:
Prospective cohorts of CPs, undergoing anticancer treatment, and healthcare workers (HCWs) were established. The participants had no history of previous COVID-19 and received either mRNA-based or adenovirus vector–based (AdV) vaccines as the primary series. Blood samples were collected before the first vaccination and after 2 weeks for each dose vaccination. Spike-specific binding antibodies (bAbs) in all participants and neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type, Delta, and Omicron variants in CPs were analyzed and presented as the geometric mean titer.
Results:
Age-matched 20 HCWs and 118 CPs were included in the analysis. The bAb seroconversion rate and antibody concentrations after the first vaccination were significantly lower in CPs than in HCWs. After the third vaccination, antibody levels in CPs with a primary series of AdV were comparable to those in HCWs, but nAb titers against the Omicron variant did not quantitatively increase in CPs with AdV vaccine as the primary series. The incidence and severity of adverse reactions post-vaccination were similar between CPs and HCWs.
Conclusion
CPs displayed delayed humoral immune response after SARS-CoV-2 vaccination. The booster dose elicited comparable bAb concentrations between CPs and HCWs, regardless of the primary vaccine type. Neutralization against the Omicron variant was not robustly elicited following the booster dose in some CPs, implying the need for additional interventions to protect them from COVID-19.
4.Erratum: Korean Practice Guidelines for Gastric Cancer 2022: An Evidencebased, Multidisciplinary Approach
Tae-Han KIM ; In-Ho KIM ; Seung Joo KANG ; Miyoung CHOI ; Baek-Hui KIM ; Bang Wool EOM ; Bum Jun KIM ; Byung-Hoon MIN ; Chang In CHOI ; Cheol Min SHIN ; Chung Hyun TAE ; Chung sik GONG ; Dong Jin KIM ; Arthur Eung-Hyuck CHO ; Eun Jeong GONG ; Geum Jong SONG ; Hyeon-Su IM ; Hye Seong AHN ; Hyun LIM ; Hyung-Don KIM ; Jae-Joon KIM ; Jeong Il YU ; Jeong Won LEE ; Ji Yeon PARK ; Jwa Hoon KIM ; Kyoung Doo SONG ; Minkyu JUNG ; Mi Ran JUNG ; Sang-Yong SON ; Shin-Hoo PARK ; Soo Jin KIM ; Sung Hak LEE ; Tae-Yong KIM ; Woo Kyun BAE ; Woong Sub KOOM ; Yeseob JEE ; Yoo Min KIM ; Yoonjin KWAK ; Young Suk PARK ; Hye Sook HAN ; Su Youn NAM ; Seong-Ho KONG
Journal of Gastric Cancer 2023;23(2):365-373
5.Impact of Coronavirus Disease 2019 on Gastric Cancer Diagnosis and Stage:A Single-Institute Study in South Korea
Moonki HONG ; Mingee CHOI ; JiHyun LEE ; Kyoo Hyun KIM ; Hyunwook KIM ; Choong-Kun LEE ; Hyo Song KIM ; Sun Young RHA ; Gyu Young PIH ; Yoon Jin CHOI ; Da Hyun JUNG ; Jun Chul PARK ; Sung Kwan SHIN ; Sang Kil LEE ; Yong Chan LEE ; Minah CHO ; Yoo Min KIM ; Hyoung-Il KIM ; Jae-Ho CHEONG ; Woo Jin HYUNG ; Jaeyong SHIN ; Minkyu JUNG
Journal of Gastric Cancer 2023;23(4):574-583
Purpose:
Gastric cancer (GC) is among the most prevalent and fatal cancers worldwide.National cancer screening programs in countries with high incidences of this disease provide medical aid beneficiaries with free-of-charge screening involving upper endoscopy to detect early-stage GC. However, the coronavirus disease 2019 (COVID-19) pandemic has caused major disruptions to routine healthcare access. Thus, this study aimed to assess the impact of COVID-19 on the diagnosis, overall incidence, and stage distribution of GC.
Materials and Methods:
We identified patients in our hospital cancer registry who were diagnosed with GC between January 2018 and December 2021 and compared the cancer stage at diagnosis before and during the COVID-19 pandemic. Subgroup analyses were conducted according to age and sex. The years 2018 and 2019 were defined as the “before COVID” period, and the years 2020 and 2021 as the “during COVID” period.
Results:
Overall, 10,875 patients were evaluated; 6,535 and 4,340 patients were diagnosed before and during the COVID-19 period, respectively. The number of diagnoses was lower during the COVID-19 pandemic (189 patients/month vs. 264 patients/month) than before it.Notably, the proportion of patients with stages 3 or 4 GC in 2021 was higher among men and patients aged ≥40 years.
Conclusions
During the COVID-19 pandemic, the overall number of GC diagnoses decreased significantly in a single institute. Moreover, GCs were in more advanced stages at the time of diagnosis. Further studies are required to elucidate the relationship between the COVID-19 pandemic and the delay in the detection of GC worldwide.
6.Korean Practice Guidelines for Gastric Cancer 2022: An Evidence-based, Multidisciplinary Approach
Tae-Han KIM ; In-Ho KIM ; Seung Joo KANG ; Miyoung CHOI ; Baek-Hui KIM ; Bang Wool EOM ; Bum Jun KIM ; Byung-Hoon MIN ; Chang In CHOI ; Cheol Min SHIN ; Chung Hyun TAE ; Chung sik GONG ; Dong Jin KIM ; Arthur Eung-Hyuck CHO ; Eun Jeong GONG ; Geum Jong SONG ; Hyeon-Su IM ; Hye Seong AHN ; Hyun LIM ; Hyung-Don KIM ; Jae-Joon KIM ; Jeong Il YU ; Jeong Won LEE ; Ji Yeon PARK ; Jwa Hoon KIM ; Kyoung Doo SONG ; Minkyu JUNG ; Mi Ran JUNG ; Sang-Yong SON ; Shin-Hoo PARK ; Soo Jin KIM ; Sung Hak LEE ; Tae-Yong KIM ; Woo Kyun BAE ; Woong Sub KOOM ; Yeseob JEE ; Yoo Min KIM ; Yoonjin KWAK ; Young Suk PARK ; Hye Sook HAN ; Su Youn NAM ; Seong-Ho KONG ;
Journal of Gastric Cancer 2023;23(1):3-106
Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.
7.The Incidence of Deep Vein Thrombosis after Various Types of Knee Surgery
Minkyu SHIN ; Hong Gi PARK ; Beom Koo LEE
The Journal of the Korean Orthopaedic Association 2022;57(1):53-58
Purpose:
The purpose of this study was to evaluate the incidence of deep vein thrombosis (DVT) after various types of knee surgery and to identify patients at high risk.
Materials and Methods:
This retrospective was conducted using the medical records of knee surgeries conducted by one surgeon at Gachon University Gil Medical Center between May 2019 and December 2020. The occurrence of DVT was determined by venous ultrasonography 4 to 6 days after surgery, and the incidence of DVT was determined for arthroscopic ligament surgery, arthroscopic meniscus surgery, arthroplasty, and osteotomy. Patients diagnosed with DVT were treated with a pharmacological agent for 3 months, and DVT was reevaluated by Doppler sonography at 3 months postoperatively.
Results:
Among a total of 221 cases, 75 cases (33.9%) were diagnosed with DVT. The incidence of DVT was significantly dependent on type of surgery, that is, anterior cruciate ligament surgery (ACL) 29.4%, meniscus surgery 30.2%, artroplasty 33.3%, and osteotomy 52.4%. In 60 of the 75 cases, DVT was successfully managed without complication by pharmacologic treatment. On the other hand, in 3 cases, pharmacologic treatment was stopped due to side effects. The other 15 cases were managed conservatively. A significant correlation was found between tourniquet application and incidence of DVT, and in the arthroplasty group, age and DVT were significantly correlated. However, surgical time was not correlated with DVT.
Conclusion
The incidence of DVT after knee surgery is significantly dependent on type of surgery. We believe that the absence of any severe complication, such as systemic or pulmonary embolism, related to DVT was due to early detection and adequate pharmaceutical management. Furthermore, we recommend that tourniquet not to be applied to patients at high risk of DVT.
8.Guidelines for Cancer Care during the COVID-19 Pandemic in South Korea
Jii Bum LEE ; Minkyu JUNG ; June Hyuk KIM ; Bo Hyun KIM ; Yeol KIM ; Young Seok KIM ; Byung Chang KIM ; Jin KIM ; Sung Ho MOON ; Keon-Uk PARK ; Meerim PARK ; Hyeon Jin PARK ; Sung Hoon SIM ; Hong Man YOON ; Soo Jung LEE ; Eunyoung LEE ; June Young CHUN ; Youn Kyung CHUNG ; So-Youn JUNG ; Jinsoo CHUNG ; Eun Sook LEE ; Hyun Cheol CHUNG ; Tak YUN ; Sun Young RHA
Cancer Research and Treatment 2021;53(2):323-329
At the end of 2019, the cause of pneumonia outbreaks in Wuhan, China, was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In February 2020, the World Health Organization named the disease cause by SARS-CoV-2 as coronavirus disease 2019 (COVID-19). In response to the pandemic, the Korean Cancer Association formed the COVID-19 task force to develop practice guidelines. This special article introduces the clinical practice guidelines for cancer patients which will help oncologists best manage cancer patients during the COVID-19 pandemic.
9.Cancer Survivors with Low Hand Grip Strength Have Decreased Quality of Life Compared with Healthy Controls: The Korea National Health and Nutrition Examination Survey 2014–2017
Hyunji KIM ; Sunmi YOO ; Hyoeun KIM ; Seung Guk PARK ; Minkyu SON
Korean Journal of Family Medicine 2021;42(3):204-211
Background:
Cancer survivors experience decreased physical function and reduced muscle strength, which leads to lower quality of life (QOL). The hand grip strength (HGS) can be a predictor of poor health-related QOL as a parameter of sarcopenia. The purpose of this study was to investigate the relationship between low HGS and QOL in cancer survivors and healthy controls.
Methods:
We analyzed 392 cancer survivors and 1,176 healthy controls from the Korea National Health and Nutrition Examination Survey, 2014–2017. We defined low HGS as 2 standard deviation values for healthy young Korean adults from a previous study. QOL was evaluated using the European Quality of Life Scale-Five Dimensions. A complex sample logistic regression model was used to assess the relationship between each dimension of low HGS and QOL.
Results:
The odds ratios (ORs) for decreased QOL were significantly higher in male cancer survivors with low HGS on self-care (OR, 8.51; 95% confidence interval [CI], 1.69–42.83) and usual activities (OR, 6.63; 95% CI, 1.22–36.03). The ORs for problems in mobility (OR, 5.87; 95% CI, 2.04–16.91), usual activities (OR, 14.46; 95% CI, 3.84–54.44), pain/discomfort (OR, 4.90; 95% CI, 2.00–12.01), and anxiety/depression (OR, 6.43; 95% CI, 2.16–19.12) were significantly high in female cancer survivors with low HGS. However, healthy controls showed no significant relationship between low HGS and QOL.
Conclusion
For cancer survivors, low HGS was associated with poor QOL in some domains. Strategies to increase muscle strength must be considered to improve the QOL of cancer survivors.
10.Guidelines for Cancer Care during the COVID-19 Pandemic in South Korea
Jii Bum LEE ; Minkyu JUNG ; June Hyuk KIM ; Bo Hyun KIM ; Yeol KIM ; Young Seok KIM ; Byung Chang KIM ; Jin KIM ; Sung Ho MOON ; Keon-Uk PARK ; Meerim PARK ; Hyeon Jin PARK ; Sung Hoon SIM ; Hong Man YOON ; Soo Jung LEE ; Eunyoung LEE ; June Young CHUN ; Youn Kyung CHUNG ; So-Youn JUNG ; Jinsoo CHUNG ; Eun Sook LEE ; Hyun Cheol CHUNG ; Tak YUN ; Sun Young RHA
Cancer Research and Treatment 2021;53(2):323-329
At the end of 2019, the cause of pneumonia outbreaks in Wuhan, China, was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In February 2020, the World Health Organization named the disease cause by SARS-CoV-2 as coronavirus disease 2019 (COVID-19). In response to the pandemic, the Korean Cancer Association formed the COVID-19 task force to develop practice guidelines. This special article introduces the clinical practice guidelines for cancer patients which will help oncologists best manage cancer patients during the COVID-19 pandemic.

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