Persistence and enrichment of dominant T cell clonotypes in expanded tumor-infiltrating lymphocytes of breast cancer.

BACKGROUND: Adoptive cell therapy using tumor-infiltrating lymphocytes (TILs) has shown promising results in cancer treatment, including breast cancer. However, clonal dynamics and clinical significance of TIL expansion ex vivo remain poorly understood. METHODS: We investigated T cell receptor (TCR) repertoire changes in expanded TILs from 19 patients with breast cancer. We compared TCR repertoire of TILs at different stages of expansion, including initial (2W TILs) and rapid expansion (REP TILs), and their overlap with formalin fixed paraffin embedded (FFPE) and peripheral blood. Additionally, we examined differences in TCR repertoire between CD4+ and CD8+ REP TILs. RESULTS: In descending order of proportion, average of 60% of the top 10% clonotypes of FFPE was retained in 2W TIL (60% in TRB, 64.7% in TRA). Among the overlapped clonotypes between 2W TILs and REP TILs, 69.9% was placed in top 30% of 2W TIL. The proportion of clonotypes in 2W TIL and REP TIL showed a significant positive correlation. CD4+ and CD8+ T cells show similar results in diversity and CDR3 length. CONCLUSIONS: Our study traces the changes in TILs repertoire from FFPE to 2W TIL and REP TIL and confirmed that clonotypes with high frequencies in TILs have a high likelihood of maintaining their priority throughout culture process.

The Effect of Roflumilast on Lipopolysaccharide-induced Acute Lung Injury During Neutropenia Recovery in Mice.

BACKGROUND/AIM: Patients with pneumonia after prolonged neutropenia are at increased risk for acute respiratory distress syndrome (ARDS). The key molecule of endothelial barrier breakdown in sepsis is lipopolysaccharide (LPS), which is a component of the outer membrane of gram-negative bacterial cell walls. Maintaining increased cyclic adenosine monophosphate (cAMP) levels in endothelial cells is effective in preventing endothelial dysfunction and microvascular permeability. The aim of this study was to elucidate whether roflumilast, a phosphodiesterase-4 (PDE-4) inhibitor, is effective in LPS-induced acute lung injury (ALI) during neutropenia recovery in a murine model. MATERIALS AND METHODS: To induce neutropenia, all mice were administered intraperitoneal cyclophosphamide. On day 2 after neutropenia, mice were administered LPS by intra-tracheal instillation. In the prevention group, roflumilast was given orally on day 0, when neutropenia was induced. In the treatment group, roflumilast was administered orally 1 hour after LPS injection. RESULTS: Roflumilast attenuated histopathological changes associated with LPS-induced lung injury. The accumulation of neutrophils and the concentrations of inflammatory cytokines IL-1ß, TNF-α, and IL-6 in bronchoalveolar lavage fluids were inhibited effectively by roflumilast. Also, MMP-9 and TGF-ß expression was attenuated in the roflumilast group. CONCLUSION: Roflumilast significantly attenuated LPS-induced ALI during neutropenia recovery.

Analysis and Development of Antigen-specific T Cells Derived from Peripheral Blood Mononuclear Cells of Healthy Donors.

BACKGROUND/AIM: Adoptive cell therapy using antigen-specific T cells is a promising treatment modality for cancer patients. Various methods to isolate specific T cells and identify corresponding T cell receptor (TCR) sequences are known. This study aimed to identify antigen-specific TCR from T cells isolated using carboxyfluorescein succinimidyl ester (CFSE), which marks proliferating activated T cells. MATERIALS AND METHODS: CFSE stained healthy donor peripheral blood mononuclear cells (PBMCs) were treated with cytomegalovirus (CMV) or Epstein-Barr virus (EBV) peptides for seven days. Then, proliferating T cells with decreased CFSE staining were isolated and single cell VDJ sequencing was performed on isolated T cells to identify antigen-specific TCRs. RESULTS: As antigen-specific TCR candidates, ten TCR clones were selected for the CMV antigen and five for the EBV antigen. The reactivity of ten CMV TCR-transduced T cells and one EBV TCR-transduced T cell toward T2 cells pulsed with CMV or EBV peptide was confirmed via NFAT-luciferase, IFN-γ ELISA, and cytotoxicity assays. CONCLUSION: Identification of antigen-specific TCRs with CFSE staining is a valid method for the development of effective immunotherapy. The identified CMV- or EBV-specific TCRs can be used for adoptive cell therapy to treat cancer.

Impact of coronavirus disease 2019 on cancer care: How the pandemic has changed cancer utilization and expenditures.

PURPOSE: Since identified in December 2019, the novel coronavirus disease 2019 (COVID-19) has had a global impact on medical resource use and costs for patients with cancer in South Korea. This study aimed to identify the medical use and costs among patients with cancer during the COVID-19 pandemic, to predict these patterns in South Korea in the future. METHODS: We conducted a secondary claims data analysis using the National Health Insurance Service database for the calendar period of 2019-2020. Monthly relative percent changes in cancer incidence, medical use, and billing costs for medical care utilization by cancer type were calculated. Then, the medical use and costs after January 2020 were predicted using a time series model with data before the COVID-19 outbreak (2014-2019). RESULTS: The incidence of cancer diagnoses has seen a notable decline since the outbreak of the COVID-19 in 2020 as compared to 2019. Despite the impact of COVID-19, there hasn't been a distinct decline in outpatient utilization when compared to inpatient utilization. While medical expenses for both inpatient and outpatient visits have slightly increased, the number of patients treated for cancer has decreased significantly compared to the previous year. In June 2020, overall outpatient costs experienced the highest increase (21.1%), while individual costs showed the most significant decrease (-4.9%) in June 2020. Finally, the number of hospitalisations and outpatient visits increased slightly from June-July in 2020, reducing the difference between the actual and predicted values. The decrease in the number of inpatient hospitalisations (-22~-6%) in 2020 was also high. CONCLUSIONS: The overall use of medical services by patients with cancer decreased in 2020 compared with that in the pre-COVID-19 pandemic period. In the future, the government should consider how to recover from the COVID-19 pandemic, and establish permanent health policies for patients with cancer.

How should the healthcare system support cancer survivors? Survivors' and health professionals' expectations and perception on comprehensive cancer survivorship care in Korea: a qualitative study.

BACKGROUND: Qualitative research on cancer survivors' need for comprehensive cancer survivorship care within the health care system is limited. Our study aimed to understand cancer survivors' and health professionals' expectations and perceptions for developing a comprehensive cancer survivorship care system in South Korea. METHODS: An exploratory qualitative study was conducted. A total of 16 subjects (11 cancer survivors and 5 health professionals) were purposively sampled from Regional Cancer Survivorship Centers or Cancer Survivor Clinics in Korea. In-depth semi-structured online or face-to-face interviews were conducted. Six steps of thematic analysis were used to analyze data. RESULTS: The following four primary themes emerged from the interviews: 1) introducing a customized follow-up care system to improve continuity of survivorship care, 2) implementing educational strategies for both survivors and health professionals to manage changed health, and 3) accepting cancer survivors as companions. These three themes included a total of nine subthemes. As a result, the comprehensive survivorship model identified needs in terms of 1) changes in the medical healthcare system and core services that can accommodate the cancer survivors' condition and 2) necessary care services and social support for cancer survivors. CONCLUSIONS: This study identified the existing gaps in Korea's current healthcare system regarding comprehensive cancer survivorship care for cancer survivors. Further research on eHealth-based counseling and educational support, the payment models of cancer survivorship care within universal health coverage, and changing social perceptions to strengthen the biopsychosocial needs of cancer survivors is needed.

The Multidomain Metaverse Cancer Care Digital Platform: Development and Usability Study.

BACKGROUND: As cancer treatment methods have diversified and the importance of self-management, which lowers the dependence rate on direct hospital visits, has increased, effective cancer care education and management for health professionals and patients have become necessary. The metaverse is in the spotlight as a means of digital health that allows users to engage in cancer care education and management beyond physical constraints. However, it is difficult to find a multipurpose medical metaverse that can not only be used in the field but also complements current cancer care. OBJECTIVE: This study aimed to develop an integrated metaverse cancer care platform, Dr. Meta, and examine its usability. METHODS: We conducted a multicenter, cross-sectional survey between November and December 2021. A descriptive analysis was performed to examine users' experiences with Dr. Meta. In addition, a supplementary open-ended question was used to ask users for their suggestions and improvements regarding the platform. RESULTS: Responses from 70 Korean participants (male: n=19, 27% and female: n=51, 73%) were analyzed. More than half (n=37, 54%) of the participants were satisfied with Dr. Meta; they responded that it was an interesting and immersive platform (n=50, 72%). Less than half perceived no discomfort when using Dr. Meta (n=34, 49%) and no difficulty in wearing and operating the device (n=30, 43%). Furthermore, more than half (n=50, 72%) of the participants reported that Dr. Meta would help provide non-face-to-face and noncontact services. More than half also wanted to continue using this platform in the future (n=41, 59%) and recommended it to others (n=42, 60%). CONCLUSIONS: We developed a multidomain metaverse cancer care platform that can support both health professionals and patients in non-face-to-face cancer care. The platform was uniquely disseminated and implemented in multiple regional hospitals and showed the potential to perform successful cancer care.

Current Status and Physicians' Perspectives of Childhood Cancer Survivorship in Korea: A Nationwide Survey of Pediatric Hematologists/Oncologists.

BACKGROUND: Data on the status of long-term follow-up (LTFU) care for childhood cancer survivors (CCSs) in Korea is lacking. This study was conducted to evaluate the current status of LTFU care for CCSs and relevant physicians' perspectives. METHODS: A nationwide online survey of pediatric hematologists/oncologists in the Republic of Korea was undertaken. RESULTS: Overall, 47 of the 74 board-certified Korean pediatric hematologists/oncologists currently providing pediatric hematology/oncology care participated in the survey (response rate = 63.5%). Forty-five of the 47 respondents provided LTFU care for CCSs five years after the completion of primary cancer treatment. However, some of the 45 respondents provided LTFU care only for CCS with late complications or CCSs who requested LTFU care. Twenty of the 45 respondents oversaw LTFU care for adult CCSs, although pediatric hematologists/oncologists experienced more difficulties managing adult CCSs. Many pediatric hematologists/oncologists did not perform the necessary screening test, although CCSs had risk factors for late complications, mostly because of insurance coverage issues and the lack of Korean LTFU guidelines. Regarding a desirable LTFU care system for CCSs in Korea, 27 of the 46 respondents (58.7%) answered that it is desirable to establish a multidisciplinary CCSs care system in which pediatric hematologists/oncologists and adult physicians cooperate. CONCLUSION: The LTFU care system for CCS is underdeveloped in the Republic of Korea. It is urgent to establish an LTFU care system to meet the growing needs of Korean CCSs, which should include Korean CCSs care guidelines, provider education plans, the establishment of multidisciplinary care systems, and a supportive national healthcare policy.

Mortality risk according to smoking trajectories after cancer diagnosis among Korean male cancer survivors: A population-based cohort study.

INTRODUCTION: Previous research on post-diagnosis smoking among cancer survivors mainly relied on smoking status, which may not fully reflect the impact of changes in smoking levels. This study aimed to evaluate mortality risk according to smoking trajectories among Korean male cancer survivors, using a trajectory approach to comprehensively capture smoking patterns. METHODS: The study included 110555 men diagnosed with cancer between 2002 and 2018 from the Korean National Health Information Database. Group-based trajectory modelling was used to identify post-diagnosis smoking trajectories among pre-diagnosis current smokers (n=45331). Cox hazards models were fitted to evaluate mortality risk according to smoking trajectories for pooled cancers, pooled smoking-related cancers, smoking-unrelated cancers, and gastric, colorectal, liver, and lung cancers. RESULTS: Smoking trajectories included light-smoking quitters, heavy-smoking quitters, consistent moderate smokers, and decreasing heavy smokers. Smoking significantly increased all-cause and cancer mortality risks in cancer patients for pooled cancers, pooled smoking-related cancers, and pooled smoking-unrelated cancers. Compared to non-smokers, all-cause mortality risk for pooled cancers significantly increased according to smoking trajectories:(AHR=1.33; 95% CI: 1.27-1.40), (AHR=1.39; 95% CI: 1.34-1.44), (AHR=1.44; 95% CI: 1.34-1.54), and (AHR=1.47; 95% CI: 1.36-1.60), respectively. Smoking increased all-cause and cancer mortality risks in gastric and colorectal cancer patients and cancer-specific mortality in lung cancer patients. The significant associations of smoking trajectories with all-cause and cancer mortality risks were primarily observed in 5-year survivors but not in short-term survivors. Among heavy smokers, smoking cessation significantly reduced all-cause mortality risk in the long-term. CONCLUSIONS: The post-diagnosis smoking trajectory independently predicts cancer prognosis among male cancer patients. Proactive cessation support should be strengthened, particularly for those who smoke heavily.

The lived experience of colorectal cancer patients with a temporary ileostomy and the patient's perception of the ostomy nurses' educational interventions.

PURPOSE: This study is aimed at exploring the lived experiences of colorectal cancer patients regarding temporary ileostomy and the educational interventions of ostomy nurses. METHODS: This study is conducted using Heideggerian phenomenological focus group. Focus group interviews were conducted from November 2021 to February 2022 using a semi-structured guide with nine colorectal cancer patients having a temporary ileostomy. The interview data were analyzed using latent content analysis RESULTS: Four main categories and 13 sub-categories are identified as the result of data analysis. Main categories were "colorectal cancer and ileostomy: patient's adaptation," "supporting resources for the patient with ileostomy," "ileostomy closure: hope and concerns," and "ostomy nurse's professionalism." The main categories reflect the shared experiences and perceptions of colorectal cancer patients, across the timeline from colorectal cancer diagnosis to ileostomy closure. CONCLUSION: This study provides a timely response to a pilot project for recognizing ostomy nurse's education for patients with stomas. Also, the findings of this study contribute to nursing knowledge by providing patients' perspectives on the education provided to them by the ostomy nurse. Lastly, this study inspires future studies to evaluate and recognize ostomy nurse's practice by using various methodological approaches.

Establishing Patient-Derived Cancer Cell Cultures and Xenografts in Biliary Tract Cancer.

PURPOSE: Biliary tract cancers (BTCs) are rare and show a dismal prognosis with limited treatment options. To improve our understanding of these heterogeneous tumors and develop effective therapeutic agents, suitable preclinical models reflecting diverse tumor characteristics are needed. We established and characterized new patient-derived cancer cell cultures and patient-derived xenograft (PDX) models using malignant ascites from five patients with BTC. MATERIALS AND METHODS: Five patient-derived cancer cell cultures and three PDX models derived from malignant ascites of five patients with BTC, AMCBTC-01, -02, -03, -04, and -05, were established. To characterize the models histogenetically and confirm whether characteristics of the primary tumor were maintained, targeted sequencing and histopathological comparison between primary tissue and xenograft tumors were performed. RESULTS: From malignant ascites of five BTC patients, five patient-derived cancer cell cultures (100% success rate), and three PDXs (60% success rate) were established. The morphological characteristics of three primary xenograft tumors were compared with those of matched primary tumors, and they displayed a similar morphology. The mutated genes in samples (models, primary tumor tissue, or both) from more than one patient were TP53 (n=2), KRAS (n=2), and STK11 (n=2). Overall, the pattern of commonly mutated genes in BTC cell cultures was different from that in commercially available BTC cell lines. CONCLUSION: We successfully established the patient-derived cancer cell cultures and xenograft models derived from malignant ascites in BTC patients. These models accompanied by different genetic characteristics from commercially available models will help better understand BTC biology.

The Insignificant Correlation between Androgen Deprivation Therapy and Incidence of Dementia Using an Extension Survival Cox Hazard Model and Propensity-Score Matching Analysis in a Retrospective, Population-Based Prostate Cancer Registry.

This study aims to evaluate the effect of androgen-deprivation therapy (ADT) on the incidence of dementia, after considering the time-dependent survival in patients with prostate cancer (PC) using a Korean population-based cancer registry database. After excluding patients with cerebrovascular disease and dementia before or within the 3-month-ADT and those with surgical castration, 9880 (19.3%) patients were matched into ADT and non-ADT groups using propensity-score matching (PSM) among 51,206 patients registered between 2006 and 2013. To define the significant relationship between ADT duration and the incidence of dementia, the extension Cox proportional hazard model was used with p-values < 0.05 regarded as statistically significant. The mean age and survival time were 67.3 years and 4.33 (standard deviation [SD] 2.16) years, respectively. A total of 2945 (9.3%) patients developed dementia during the study period, including Parkinson's (11.0%), Alzheimer's (42.6%), vascular (18.2%), and other types of dementia (28.2%). Despite PSM, the PC-treatment subtypes, survival rate, and incidence of dementia significantly differed between the ADT and non-ADT groups (p < 0.05), whereas the rate of each dementia subtype did not significantly differ (p = 0.069). A multivariate analysis for dementia incidence showed no significance of ADT type or use duration among patients with PC (p > 0.05), whereas old age, obesity, regional SEER stage, a history of cerebrovascular disease, and a high Charlson Comorbidity Index were significant factors for dementia (p < 0.05). Insignificant correlation was observed between ADT and the incidence of dementia based on the extension survival model with PSM among patients with PC.

How Bereaved Parents Experience Public, Self Stigma Years After a Child's Death.

This study identifies the stigma experienced by 12 bereaved parents 2 and 5 years after losing a child in the Sewol ferry disaster in South Korea. Using thematic analysis, we categorized the experience of stigma into two components based on Corrigan and Kosyluk's social cognitive model of stigma: public stigma and self-stigma, and each was analyzed into three types of stigma: stereotype, prejudice, and discrimination. We identified four additional factors related to stigma mitigation. The potential implications for characterizing the experiences of bereaved parents, particularly those facing stigma, are discussed in light of these findings in the longitudinal perspective.

The Positive Effects of Cancer Survivor Support Service on Distress in South Korea: A Nationwide Prospective Study.

BACKGROUND AND AIM: Cancer survivors are gradually increasing, however, they suffer from various difficulties. We aimed to investigate the characteristics of cancer survivors and the effects of the services of the Korean Cancer Survivorship Center Pilot Project launched by the South Korean government on distress. METHODS: A prospective observational cohort study was performed on cancer survivors who completed primary treatment. Cancer survivors' distress and symptoms such as fatigue, pain, depressive mood, anxiety, and insomnia were evaluated by well-trained nurses. Regarding their needs, medical and psychosocial support services were provided. RESULTS: This study included 1,921 cancer survivors, with a mean age of 57.3 years (68.7% females). Breast cancer was most common, followed by stomach and colorectal cancer. Psychosocial and medical support decreased the percentage of the high-distress group from 50.9 to 30.5% and decreased the percentage of cancer survivors with high scores in fatigue, pain, anxiety, depressive mood, and insomnia. The independent predictors of a low distress level after the use of the services were older age, the relief of fatigue, pain, and insomnia. CONCLUSION: This study showed that psychosocial and medical support is associated with the lower distress and physical and mental symptoms of cancer survivors. Psychosocial and medical support could contribute to distress relief in cancer survivors. Further management strategies for fatigue, pain and insomnia are required.

Examining the Effectiveness of the Discharge Plan Model on the South Korean Patients with Cancer Completed Cancer Treatment and Are Returning to the Community: A Pilot Study.

This study aimed to examine the effectiveness of a discharge plan model for South Korean patients with cancer who had completed treatment and were returning to the community. Overall, 23 patients with cancer were recruited at the National Cancer Center in Goyang-si. The effectiveness of the discharge plan was examined using four methods: Social Needs Screening Toolkit (2018), early screening for discharge plan, current life situation v.2.0, and a questionnaire regarding problems after discharge from the hospital. Subsequently, the results were analyzed using descriptive statistical analysis methods with the Stata 14.0 program. The largest age group of study participants was between 45 and 64 years. No participants responded to urgent needs, whereas nine (39.13%) participants needed support for their social needs. According to the in-depth evaluation of participants, more than 80% of the respondents answered that patients with cancer needed no help in self-management, daily living activities, or mental health. The satisfaction survey results showed that the degree to which the "discharge plan" was helpful for health management at home after discharge was 4.41 of 5, and the degree to which it helped return to daily life was 3.86 of 5.

Phenotypic Differences of CD103+ Tissue-Resident Memory T Cells Associated with Various Cancers.

BACKGROUND/AIMS: The presence and clinical importance of tissue-resident memory T (TRM) cells have been recently described in association with various cancer types. However, the frequency and the traditional naïve-effector-memory phenotypic characteristics of TRM cells are largely unknown. METHODS: We analyzed single-cell populations of colorectal cancer (CC, n = 18), stomach cancer (SC, n = 13), renal cell carcinoma (RCC, n = 19), and breast cancer (BC, n = 16) by dissociation of tumor tissue with collagenase/hyaluronidase. We investigated populations of naïve, effector, and memory T and TRM cells by flow cytometry. RESULTS: Among CD8- cells, CC was associated with a significantly higher proportion of CD103+ T cells than other tumor types (p < 0.001). Among CD8+ cells, CC and SC were associated with higher CD103+ T-cell proportions than RCC and BC (p < 0.001). Significantly more CD8+ than CD8- cells expressed CD103 (p < 0.001). In association with SC, RCC, and BC, CD8+ T cells had a similar T-cell phenotype composition pattern: fewer effector T cells and more memory-type T cells among CD103+ cells compared with CD103- cells (p < 0.05). Tumors with higher proportion of CD103+ cells had no specific clinicopathologic characteristics than those with lower proportion of CD103+ cells. CONCLUSION: TRM cell abundance and phenotypes varied among CC, SC, RCC, and BC. Further studies regarding the functional differences of TRM associated with various tumors are warranted.

Validation of Cancer Diagnosis Based on the National Health Insurance Service Database versus the National Cancer Registry Database in Korea.

PURPOSE: This study aimed to assess the feasibility of operational definitions of cancer patients in conducting cancer-related studies using the claims data from the National Health Insurance Service (NHIS). MATERIALS AND METHODS: Cancer incidence data were obtained from the Korean Central Cancer Registry, the NHIS primary diagnosis, and from the rare and intractable disease (RID) registration program. RESULTS: The operational definition with higher sensitivity for cancer patient verification was different by cancer type. Using primary diagnosis, the lowest sensitivity was found in colorectal cancer (91.5%; 95% confidence interval [CI], 91.7 to 92.0) and the highest sensitivity was found in breast cancer (97.9%; 95% CI, 97.8 to 98.0). With RID, sensitivity was the lowest in liver cancer (91.9%; 95% CI, 91.7 to 92.0) and highest in breast cancer (98.1%; 95% CI, 98.0 to 98.2). In terms of the difference in the date of diagnosis in the cancer registration data, > 80% of the patients showed a < 31-day difference from the RID definition. CONCLUSION: Based on the NHIS data, the operational definition of cancer incidence is more accurate when using the RID registration program claims compared to using the primary diagnosis despite the relatively lower concordance by cancer type requires additional definitions such as treatment.

The Association of Estrogen Receptor Activity, Interferon Signaling, and MHC Class I Expression in Breast Cancer.

PURPOSE: The expression of major histocompatibility complex class I (MHC I) has previously been reported to be negatively associated with estrogen receptor (ER) expression. Furthermore, MHC I expression, level of tumor-infiltrating lymphocytes (TILs), and expression of interferon (IFN) mediator MxA are positively associated with one another in human breast cancers. This study aimed to investigate the mechanisms of association of MHC I with ER and IFN signaling. MATERIALS AND METHODS: The human leukocyte antigen (HLA)-ABC protein expression was analyzed in breast cancer cell lines. The expressions of HLA-A and MxA mRNAs were analyzed in MCF-7 cells in Gene Expression Omnibus (GEO) data. ER and HLA-ABC expressions, Ki-67 labeling index and TIL levels in tumor tissue were also analyzed in ER+/ human epidermal growth factor receptor 2 (HER2)- breast cancer patients who randomly received either neoadjuvant chemotherapy or estrogen modulator treatment followed by resection. RESULTS: HLA-ABC protein expression was decreased after ß-estradiol treatment or hESR-GFP transfection and increased after fulvestrant or IFN-γ treatment in cell lines. In GEO data, HLA-A and MxA expression was increased after ESR1 shRNA transfection. In patients, ER Allred score was significantly lower and the HLA-ABC expression, TIL levels, and Ki-67 were significantly higher in the estrogen modulator treated group than the chemotherapy treated group. CONCLUSION: MHC I expression and TIL levels might be affected by ER pathway modulation and IFN treatment. Further studies elucidating the mechanism of MHC I regulation could suggest a way to boost TIL influx in cancer in a clinical setting.

A Comparative Analysis of the Perception of Cancer Patients and Healthcare Providers (Oncology Physicians, Nurses, Social Workers) in Support of Integrated Community-Linked Cancer Plans.

This study aimed to examine the awareness and status of cancer patients and healthcare providers (physicians, nurses and social workers) regarding community linkage, in order to establish a desirable care plan model in a future research project. The survey was conducted via two methods: face-to-face for cancer patients (n = 308) and oncology physicians (n = 210), and due to COVID-19 circumstances, online for nurses (n = 200) and social workers (n = 313). As a result, more than 95% of the healthcare providers responded that cancer patients required community-linked services and discharge plans, whereas 50.7% and 79.2% of cancer patients noted the importance of community-linked services and discharge plans, respectively. Social workers, among healthcare providers, showed the most positive experience about connecting patients to community services since 69.7% of them responded as "excellent". However, as a group, cancer patients considered the necessity of community-linked service as less important, as only 50.7% responded as agreeing it was necessary. The barriers to community linkage were the lack of communication among the different professions of healthcare providers, and the ambiguity in their roles. The findings of this study will inform future community-linked health research, policies and systems for cancer patients. In particular, an in-depth interview with cancer patients will be required to explore their lack of acknowledgment about the necessity of community-linked services. Therefore, this study is expected to contribute to the improvement and supplementation of cancer policies.

A New Human Leukocyte Antigen Typing Algorithm Combined With Currently Available Genotyping Tools Based on Next-Generation Sequencing Data and Guidelines to Select the Most Likely Human Leukocyte Antigen Genotype.

Background: High-precision human leukocyte antigen (HLA) genotyping is crucial for anti-cancer immunotherapy, but existing tools predicting HLA genotypes using next-generation sequencing (NGS) data are insufficiently accurate. Materials and Methods: We compared availability, accuracy, correction score, and complementary ratio of eight HLA genotyping tools (OptiType, HLA-HD, PHLAT, seq2HLA, arcasHLA, HLAscan, HLA*LA, and Kourami) using 1,005 cases from the 1000 Genomes Project data. We created a new HLA-genotyping algorithm combining tools based on the precision and the accuracy of tools' combinations. Then, we assessed the new algorithm's performance in 39 in-house samples with normal whole-exome sequencing (WES) data and polymerase chain reaction-sequencing-based typing (PCR-SBT) results. Results: Regardless of the type of tool, the calls presented by more than six tools concordantly showed high accuracy and precision. The accuracy of the group with at least six concordant calls was 100% (97/97) in HLA-A, 98.2% (112/114) in HLA-B, 97.3% (142/146) in HLA-C. The precision of the group with at least six concordant calls was over 98% in HLA-ABC. We additionally calculated the accuracy of the combination tools considering the complementary ratio of each tool and the accuracy of each tool, and the accuracy was over 98% in all groups with six or more concordant calls. We created a new algorithm that matches the above results. It was to select the HLA type if more than six out of eight tools presented a matched type. Otherwise, determine the HLA type experimentally through PCR-SBT. When we applied the new algorithm to 39 in-house cases, there were more than six matching calls in all HLA-A, B, and C, and the accuracy of these concordant calls was 100%. Conclusions: HLA genotyping accuracy using NGS data could be increased by combining the current HLA genotyping tools. This new algorithm could also be useful for preliminary screening to decide whether to perform an additional PCR-based experimental method instead of using tools with NGS data.