Search

Background The hormone receptor (HR)-positive metastatic breast cancer (MBC) patients show a diverse range of tumor mutational burden (TMB), but its biological and clinical implication has been largely unrevealed. Here we report genomic landscape of 117 HR+ MBC patients who were included in the pre-screening tissue genomic analysis of MUTATION-1 study (SABCS 2021; Abs P1-19-03) according to TMB of tumors. Patients and method The MUTATION-1 study (NCT03608865) enrolled HR-positive MBC patients who received prior ≥ 1 line of systemic therapy, and performed prescreening with whole exome sequencing (WES) and RNA-seq of fresh-frozen tissue of metastatic or recurred tumors. Patients who met upper 30% of TMB were eligible for treatment phase and received durvalumab plus tremelimumab. This study analyzed 117 prescreening tissues of MUTATION-1 study patients for mutation and transcriptomic landscape analysis. (WES, n=117; RNA-seq, n=107) Results The 117 patients showed diverse TMB (range 0~21.7 mut/Mb, median 2.0 mut/Mb) and genomic alterations. The most frequently mutated gene included PIK3CA (29.1%), TP53 (27.4%), ESR1 (23.9%), GATA3 (19.7%), and MAP3K1 (12.0%). There was no association between patient survival and TMB. We estimated single base substitution (SBS) mutational signature of patients with SigMA algorithm. The patients were classified according to their dominant mutational signatures: APOBEC (25.6%), HRD (41.0%), clockwise (28.2%), SBS8, and SBS17. The APOBEC patients showed higher TMB (median 3.47 mut/Mb) and higher mutation prevalence in PIK3CA (63.3% vs. 29.1%), ARID1A (16.7% vs. 6.0%), and NF1 (16.7% vs. 6.8%) compared with other patients. The high TMB positively correlated with time from MBC diagnosis to biopsy. Tumors with TMB ≥ 5 mut/Mb were exclusively found in patients diagnosed as MBC ≥ 36 months before the timing of biopsy. In the matched RNA-seq analysis, TMB was higher in luminal B and HER2-enriched intrinsic subtype patients than basal or luminal A subtype. The high TMB (≥ 3.16 mut/Mb, cutoff used for treatment phase patient selection) patients showed upregulation of G2/M checkpoint, MYC, E2F1, and MTORC1 signature compared to low TMB patients. In the tumor microenvironment analysis by CIBESORT, PIK3CA mutant patients showed lower score of cytotoxic T cell than others. Conclusions The high TMB in HR+ breast cancer was associated with longer time duration from MBC diagnosis to biopsy, high APOBEC signature, and cell cycle/MYC signature gene upregulation. Further therapeutic targeting of high TMB patients is warranted based on their genomic and immunologic characteristics. Citation Format: Min Hwan Kim, Yohan Yang, Eunyoung Kim, Yong Wha Moon, Gun Min Kim, Seul-Gi Kim, Yee Soo Chae, Jieun Lee, Jae Ho Jeong, Kyung-Hun Lee, Han Jo Kim, Joo Young Jung, Su-Jin Koh, Kyoung Eun Lee, Hee-Jun Kim, Kyong Hwa Park, Seungtaek Lim, Yeon Hee Park, Sangwoo Kim, Joo Hyuk Sohn. Genomic characterization of hormone receptor-positive advanced breast cancer with high tumor mutational burden: fresh-frozen tissue genomic analysis from MUTATION-1 study (KCSG BR17-04) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-14-04.

Metastasis is the leading cause of mortality in most patients with cancer. Despite its clinical importance, mechanistic underpinnings of metastatic progression remain poorly understood. Hypoxia, a condition of insufficient oxygen availability, frequently occurs in solid tumors because of their high oxygen/nutrient demand and abnormal tumor vasculature. In this review, we describe the roles of hypoxia and hypoxia-inducible factor (HIF) signaling in the metastatic cascade, with an emphasis on recent biological insights from in vivo studies.

Adjuvant therapy; Breast cancer; Olaparib Terapia adyuvante; Cáncer de mama; Olaparib Teràpia adjuvant; Càncer de mama; Olaparib Background The randomized, double-blind OlympiA trial compared 1 year of the oral poly(adenosine diphosphate-ribose) polymerase inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2-negative, early breast cancer (EBC). The first pre-specified interim analysis (IA) previously demonstrated statistically significant improvement in invasive disease-free survival (IDFS) and distant disease-free survival (DDFS). The olaparib group had fewer deaths than the placebo group, but the difference did not reach statistical significance for overall survival (OS). We now report the pre-specified second IA of OS with updates of IDFS, DDFS, and safety. Patients and methods One thousand eight hundred and thirty-six patients were randomly assigned to olaparib or placebo following (neo)adjuvant chemotherapy, surgery, and radiation therapy if indicated. Endocrine therapy was given concurrently with study medication for hormone receptor-positive cancers. Statistical significance for OS at this IA required P < 0.015. Results With a median follow-up of 3.5 years, the second IA of OS demonstrated significant improvement in the olaparib group relative to the placebo group [hazard ratio 0.68; 98.5% confidence interval (CI) 0.47-0.97; P = 0.009]. Four-year OS was 89.8% in the olaparib group and 86.4% in the placebo group (Δ 3.4%, 95% CI −0.1% to 6.8%). Four-year IDFS for the olaparib group versus placebo group was 82.7% versus 75.4% (Δ 7.3%, 95% CI 3.0% to 11.5%) and 4-year DDFS was 86.5% versus 79.1% (Δ 7.4%, 95% CI 3.6% to 11.3%), respectively. Subset analyses for OS, IDFS, and DDFS demonstrated benefit across major subgroups. No new safety signals were identified including no new cases of acute myeloid leukemia or myelodysplastic syndrome. Conclusion With 3.5 years of median follow-up, OlympiA demonstrates statistically significant improvement in OS with adjuvant olaparib compared with placebo for gBRCA1/2pv-associated EBC and maintained improvements in the previously reported, statistically significant endpoints of IDFS and DDFS with no new safety signals. Funding for this work, which was conducted as a collaborative partnership among the Breast International Group, NRG Oncology, Frontier Science, AstraZeneca, and Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, U.S.A. (MSD), was provided by the National Institutes of Health (grant numbers: U10CA 180868, UG1CA 189867, and U10CA 180822) and by AstraZeneca as part of an alliance between AstraZeneca and MSD. Provision of olaparib and placebo was from AstraZeneca.

We investigated the efficacy and safety of a trastuzumab biosimilar, Herzuma®, in combination with treatment of physician's choice (TPC) in patients with HER2+ metastatic breast cancer (MBC) who had failed at least two HER2 directed chemotherapies.

PurposeAnalysis of circulating tumor DNA (ctDNA) in blood could allow noninvasive genetic analysis of primary tumors. Although there have been unmet needs for noninvasive methods in patients with primary central nervous system lymphoma (PCNSL), it is still not determined whether plasma ctDNA analysis could be useful for patients with PCNSL. Materials and MethodsTargeted deep sequencing of 54 genes was performed in cell-free DNA isolated from plasma samples collected pretreatment, during treatment, and at the end of treatment in 42 consecutively diagnosed PCNSL patients between January 2017 and December 2018.ResultsTargeted sequencing of plasma cell-free DNA detected somatic mutations representing ctDNA in 11 cases (11/41, 27%). The detection of ctDNA was not related to the concentration of cell-free DNA or tumor volume. The mutation profiles of these 11 cases varied between patients. The most frequently mutated gene was PIM1 (4/11, 36.4%), whereas KMT2D, PIK3CA, and MYD88 were each observed in three patients (3/11, 27%). The mutations of 13 genes were concordantly found in primary tumor tissue and plasma ctDNA, giving a detection sensitivity of 45%. During the serial tracking of seven patients with complete response, the disappearance of ctDNA mutations was found in four patients, whereas three patients had detected ctDNA mutation at the end of treatment. ConclusionThe plasma ctDNA mutation analysis still has limited value for surveillance and predicting treatment outcomes of PCNSL because the detection efficiency was lower than other systemic lymphomas. Thus, analytical platforms should be improved to overcome anatomical hurdles associated with PCNSL.

In the Concealed Information Test (CIT), differential responses between crime-relevant and crime-irrelevant items are indicative of concealed knowledge of a crime, and are used to classify an individual as either "guilty" or "innocent". However, when crime-relevant items are leaked before the test, an innocent examinee can exhibit enhanced responses to the crime-relevant items, thus causing such examinee to be wrongly classified as guilty. In an attempt to solve this problem, we examined the role of retroactive memory interference (RI) in differentiating informed innocents from guilty participants, using a P300-based CIT. Participants acquired crime-related knowledge either by committing a mock crime (guilty group) or reading a paper that described a mock crime (informed innocent group). Subsequently, the participants within each condition were randomly assigned to either an RI group, where they were exposed to new crime-related details before the CIT, or a control group. We found an interaction between guilty and RI groups: in the guilty group, there was a significant difference in P300 amplitude between the probe and irrelevant items, regardless of RI manipulation, whereas in the informed innocent group, a difference in P300 amplitude between the probe and irrelevant items was significant only in the control group, but not in the RI group. This led to an improved detection rate of the informed innocents (31% for the control group vs. 77% for the RI group). These results suggest that RI manipulation could be used to reduce the false positive outcomes of informed innocents without affecting the detection rate of guilty participants.

Supplementary Figure S1. HIF1α is dispensable for pancreas development. Supplementary Figure S2. Additional characterization of KrasG12D;Hif1αKO animals. Supplementary Figure S3. Disease spectrum of KrasG12D and KrasG12D;Hif1αKO mice. Supplementary Figure S4. Additional characterization of immune cell infiltration in KrasG12D and KrasG12D;Hif1αKO pancreata. Supplementary Figure S5. HIF1α deficiency increases the proportion of B1b cells in spleen. Supplementary Figure S6. B cell depletion inhibits development of microinvasive neoplasms in KrasG12D;Hif1αKO pancreata. Supplementary Figure S7. Characterization of pancreatic immune infiltrates following αCD20 mAb administration. Supplementary Figure S8. Effects of HIF1α on expression of cytokines and chemokines.

Background: Hormone-receptor (HR) positive breast cancer is the main subtype of breast cancer. Although overall survival of HR-positive metastatic breast cancer (MBC) patients has improved by various therapies including endocrine therapies, CDK4/6 inhibitors, and cytotoxic chemotherapy, it is still considered incurable. Immune checkpoint inhibitors have rarely been clinically tested in HR-positive breast cancer, despite proving anti-cancer activity in early and metastatic triple-negative breast cancer in various trials. We evaluated efficacy and safety of combined durvalumab and tremelimumab in the HR-positive MBC, which was enriched with high tumor mutational burden (TMB). Methods: HR-positive MBC patients who received prior 1 or more lines of therapy in metastatic setting were prescreened with whole exome sequencing (WES) using metastatic or recurred tumor biopsies. Criterion of high TMB was defined as upper 30%. In the beginning, the criterion of high TMB was 2.1 mutations per Mb, based on the retrospective WES database in Yonsei Cancer Center and this criterion was recalculated every 30 cases. Patients who met upper 30% of TMB were treated with combined durvalumab (1500mg every 4 weeks upto 13 doses) and tremelimumab (75mg every 4 weeks upto 4 doses). Response was evaluated every 2 cycles using RECIST 1.1 and toxicity was evaluated using NCI-CTCAE 4.03. Tumor-infiltrating lymphocyte (TIL) and PD-L1 expression were also analyzed to investigate a correlation with TMB. Results: Biopsies of recurrent or metastatic tumors were taken from a total of 119 patients for WES assay. A median turn-around-time of TMB data was 30.0 days (range, 16~67). Of these 119 patients, a median number of nonsynonymous mutations was 2.0 per Mb (range, 0~21.7) with upper 30% criterion of 3.1. High TMB showed a trend toward old age (P=0.074) and single positivity of estrogen receptor (ER) or progesterone receptor (PR) compared to positivity of both ER and PR (P=0.055). TMB was positively correlated with TILs (r=0.289, P=0.005). Thirty patients with high TMB received study treatment with a median 2 cycles (range, 1~13). A median prior lines of therapies in metastatic setting was 4 (range, 1~9). The objective response and clinical benefit rates were 6.3% (2 PRs of 30) and 20% (2 PRs plus 4 SDs of 30). There was one treatment-related mortality due to pneumonitis. Immune-related adverse events included endocrinopathy (n=3; hypothyroidism in 2, hyperthyroidism in 1), enteritis (n=2), skin rash (n=2), pneumonitis (n=1), and so on. Biomarker analyses are underway. Conclusions: WES-based TMB using metastatic tumor biopsy was a feasible platform to prescreen HR-positive MBC patients. Combined durvalumab and tremelimumab showed a modest activity and good tolerability in heavily treated, HR-positive MBC with high TMB. Citation Format: Yong Wha Moon, Eunyoung Kim, Min Hwan Kim, Gun Min Kim, Seul-Gi Kim, YeeSoo Chae, Jieun Lee, Jae Ho Jeong, Kyung-Hun Lee, Han Jo Kim, Joo Young Jung, Su-Jin Koh, Kyoung Eun Lee, Hee-Jun Kim, Kyong Hwa Park, Seungtaek Lim, Yeon Hee Park, Tae Hoen Kim, Sewha Kim, Yohan Yang, Sangwoo Kim, Joohyuk Sohn. Phase II trial of durvalumab and tremelimumab in the hormone receptor-positive metastatic breast cancer with high tumor mutational burden selected by whole exome sequencing: Korean cancer study group trial (KCSG BR17-04) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-19-03.

Purpose: T-DM1, an antibody-drug conjugate, has significant antitumor activity in patients with HER2-positive metastatic breast cancer (mBC) patients who had progressed after trastuzumab-based chemotherapy. This study was conducted to investigate the clinical practice and factors related with outcomes of T-DM1 use for HER2-positive mBC patients in the nation-wide real-world setting. Method: This complete enumeration study included the patients with HER2-positive mBC who received T-DM1 as palliative therapy from August 2017 to December 2018 under the registry of Health Insurance Review & Assessment Service in Korea. Safety and outcomes of T-DM1 including overall response rate (ORR), progression-free survival (PFS), and overall survival were evaluated. Factors significant in univariate analysis were analyzed in multivariate model. Result: From the sixty institutions, a total of 824 patients were enrolled. Mean age was 58 years-old, 818 patients (99.3%) were female and 516 patients (62.6%) had relapsed after curative treatment. About 40% patients received T-DM1 as first or second line treatment, 21.5% received it as third line and 37.3% as fourth or over line. During a median follow-up of 16.8 months, the ORR was 32.8%, median PFS was 7.2 months and median OS was not reached. In multivariate analysis, clinical factors associated with the lower PFS were age (< 65 year-old, hazard ratio[HR] 1.53, 95% confidence interval[CI]: 1.214-1.919, p < 0.001), poor ECOG performance status (PS ≥ 2, HR 1.98, 95% CI: 1.493-2.626, p < 0.001), previous pertuzumab use (HR 1.40, 95% CI: 1.118-1.742, p = 0.003) and previous lapatinib use (HR 1.29, 95% CI: 1.047-1.586, p =0.017). The common grade 3-4 adverse events were thrombocytopenia (13.0%), neutropenia (2.9%), and elevation of liver enzyme (2.5%). Hypokalemia (≤ 3.0 mmol/L) and any-grade bleeding event such as epistaxis and gum-bleeding occurred in 25 (3.1%) and 94 patients (11.4%), respectively. Conclusion: This is the first, nationwide, real-world data about T-DM1 use of the HER2-positive metastatic breast cancer patients in Korea. The efficacy and toxicity profile of T-DM1 in the real-world practice were comparable with those of randomized trials. Patients’ factors and previous anti-HER2 therapy could predict the outcomes of T-DM1. Further studies to reveal the subtypes of good responders to T-DM1 and the sequence of anti-HER2 therapy are warranted. Citation Format: Sun Kyung Baek, Jae-Ho Jeong, Yeon-Hee Park, Hee Kyung Ahn, Min Hwan Kim, In Hae Park, Young Ju Suh, Dae-Won Lee, Sung Hoon Sim, Jee Hyun Kim, Hyun-Jeong Shim, Yeesoo Chae, Su-Jin Koh, Hyorak Lee, Jieun Lee, Jae-Ho Byun, Youngmi Seol, Eun Mi Lee, Jin Seok Ahn, Kyung-Hae Jung, Seock-Ah Im, Keun Seok Lee, Joohyuk Sohn, Kyoung Eun Lee. A nationwide real-world study for evaluation of efficacy and safety of T-DM1 in patients with HER2-positive locally-advanced unresectable or metastatic breast cancer in Korea (KCSG BR19-15) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-18-32.

Background: Prognosis of patients with HER-2 positive metastatic breast cancer (MBC) has been revolutionized with the development of monoclonal antibodies targeting HER-2 and antibody-drug conjugate, but resistance to anti-HER-2 therapy is inevitable ultimately. PI3K-AKT-mTOR pathway aberration is known to be one of the key resistance mechanisms. BR18-13(KM-10A) study is a phase 2 clinical trial evaluating efficacy and safety of Herzuma® (trastuzumab biosimilar) plus Gedatolisib (dual PI3K/mTORC inhibitor) in patients with HER-2 positive MBC who progressed after multiple lines of therapy. Methods: Patients with HER-2 positive MBC with known PIK3CA pathologic mutation or amplification whose disease progressed after more than 2 HER-2 directed therapy were enrolled in the study. They received Herzuma® (8mg/kg IV for 1st cycle loading dose, and then 6mg/kg IV every 3 weeks) plus Gedatolisib (180mg on D1, 8, 15 of every 21 days). We evaluated efficacy of the combination treatment as interim analysis. The data cutoff of this interim analysis was June 8, 2021. Results: 17 patients were enrolled and followed for a median of 6.2 months. At data cutoff, 17 patients were eligible for response assessment. All patients were confirmed to have pathologic PIK3CA aberrations: 9 kinase mutations (H1047X), 5 helical mutations (E545X), 2 other point mutations, and 1 amplification. Overall, response rate was 64.7% and disease control rate was 82.4%. Eleven patients reached partial response (PR) as their best response, three were stable disease (SD), and three had progressive disease (PD). Two patients who have reached PR remain on investigational treatment until the data cutoff point, and the longest one is on treatment for 12.0 months. The median progression-free survival assessed in data cutoff time was 5.9 months. One patient ended treatment due to CNS disease progression, but her visceral metastatic lesions were decreased with experimental treatment. No fatal adverse events related to trial medication were reported. Conclusion: In this phase 2 study, Trastuzumab biosimilar plus Gedatolisib presented 64.7% of response rate with manageable toxicity in patients with HER-2 positive MBC with PIK3CA mutation. Clinical trial information: NCT03698383 Acknowledgement: this research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health &Welfare, Republic of Korea (Grant number: HI17C2206). Citation Format: Ju Won Kim, Hee Kyung Ahn, Jong Gwon Choi, Yee Soo Chae, Gyeong-Won Lee, Keon Uk Park, Eunmi Lee, Sung Hoon Sim, Jee Hyun Kim, Yeon Hee Park, Miso Kim, Jin Hyun Park, Jeong Eun Kim, Han Jo Kim, Mi Sun Ahn, So Yeon Oh, Min Hwan Kim, Su-Jin Koh, Kyoung Eun Lee, Myoung Joo Kang, Jae Ho Byun, Joo Young Ha, Jung Hye Kwon, Joo Young Jung, Su Ee Lee, Inhae Park, Kyong Hwa Park. Phase II study of trastuzumab biosimilar (Herzuma®) plus gedatolisib in patients with HER-2 positive metastatic breast cancer who progressed after 2 or more HER-2 directed chemotherapy (BR 18-13, KM-10A): Interim analysis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-16-03.

Purpose Certain patient subgroups who do not respond to induction chemotherapy (IC) show inherent chemoresistance in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). This study aimed to assess the prognostic value of IC, and role of IC in guiding the selection of a definitive locoregional therapy.Materials and Methods Out of the 445 patients in multi-institutional LA-HNSCC cohort, 158 (36%) receiving IC were enrolled. The study outcome was to assess overall survival (OS) through IC responsiveness and its role to select subsequent treatments.Results Among 135 patients who completed subsequent treatment following IC, 74% responded to IC (complete response in 17% and partial response in 58%). IC-non-responders showed 4.5 times higher risk of mortality than IC-responders (hazard ratio, 4.52; 95% confidence interval, 2.32 to 8.81; p < 0.001). Among IC-responders, 84% subsequently received definitive concurrent chemoradiotherapy (CCRT) and OS was not differed by surgery or CCRT (p=0.960). Regarding IC-non-responders, 54% received CCRT and 46% underwent surgery, and OS was poor in CCRT (24-month survival rate of 38%) or surgery (24-month survival rate of 63%).Conclusion Response to IC is a favorable prognostic factor. For IC-responders, either surgery or CCRT achieved similar survival probabilities. For IC-non-responder, multidisciplinary approach was warranted reflecting patients’ preference, morbidity, and prognosis.

Background/Aims: Treatment decisions for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) are complicated, and multi-modal treatments are usually indicated. However, it is challenging for older patients to complete treatments. Thus, we investigated disease characteristics, real-world treatment, and outcomes in older LA-HNSCC patients.Methods: Older patients (aged ≥ 70 years) were selected from a large nationwide cohort that included 445 patients with stage III–IVB LA-HNSCC from January 2005 to December 2015. Their data were retrospectively analyzed and compared with those of younger patients.Results: Older patients accounted for 18.7% (83/445) of all patients with median age was 73 years (range, 70 to 89). Proportions of primary tumors in the hypopharynx and larynx were higher in older patients and older patients had a more advanced T stage and worse performance status. Regarding treatment strategies of older patients, 44.5% of patients received concurrent chemoradiotherapy (CCRT), 41.0% underwent surgery, and 14.5% did not complete the planned treatment. Induction chemotherapy (IC) was administered to 27.7% (23/83) of older patients; the preferred regimen for IC was fluorouracil and cisplatin (47.9%). For CCRT, weekly cisplatin was prescribed 3.3 times more often than 3-weekly cisplatin (62.2% vs. 18.9%). Older patients had a 60% higher risk of death than younger patients (hazard ratio, 1.6; p = 0.035). Oral cavity cancer patients had the worst survival probability.Conclusions: Older LA-HNSCC patients had aggressive tumor characteristics and received less intensive treatment, resulting in poor survival. Further research focusing on the older population is necessary.

We aimed to compare treatment modalities and outcomes by gender in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC). We characterized the sex-specific differences and compared the overall survival (OS) between male and female patients in a multicenter cohort of LA-HNSCC. To minimize the observed confounding, propensity score matching was utilized. The study included 445 patients; 385 (86.5%) were men and 60 (13.5%) were women. In terms of age, smoking habits, drinking habits, and primary tumor locations, there was a significant imbalance in sex before the matching. Propensity score matching yielded 60 patient pairs, with no statistical difference between the sexes in terms of their characteristics. As for the treatment strategies, there were no significant differences between the sexes before (p = 0.260) and after (p = 0.585) the propensity score matching. When comparing the survival probabilities between the sexes, OS was not significantly different in the overall (HR 1.02; 95% CI 0.59–1.76; p = 0.938) and propensity-score-matched population (HR 1.46; 95% CI 0.68–3.17; p = 0.331). These results suggest that there was no difference in prognosis by gender in the treatment modalities and outcomes of LA-HNSCC in real-world practice.

We report 14 species of flowering plants as new additions to the flora of Laos. These are Illex viridis (Aquifoliaceae), Capparis erycibe (Capparaceae), Euphorbia bokorensis (Euphorbiaceae), Exacum darae (Gentianaceae), Aeschynanthus cambodiensis (Gesneriaceae), Tetraphyllum roseum (Gesneriaceae), Utricularia gibba (Lentibulariaceae), Macrosolen brandisianus (Loranthaceae), Decaschistia siamensis (Malvaceae), Nyssa yunnanensis (Nyssaceae), Adenia penangiana var. penangiana (Passifloraceae), Pentaphylax euryoides (Pentaphylacaceae), Wikstroemia bokorensis (Thymelaeaceae), and Debregeasia wallichiana (Urticaceae). We discovered the species during a botanical survey of the Phou Khao Khouay National Biodiversity Conservation Area (PKKNBCA) of Lao PDR in 2015-2019. In addition, nine rarely collected flowering plant species in Laos are newly reported for the PKKNBCA.

Background and PurposeFew studies have critically appraised Perceived Stress Scale (PSS) in immigrants. The purpose of the article is to determine if PSS is adequately developed and properly used with U.S. immigrants.MethodsSearching via PubMed and PsycINFO databases resulted in 10 research papers published between 2009 and 2019 that met the selection criteria and were integrated for this review.ResultsMost of the studies do not have adequate theoretical models and do not have proper consideration of socio-cultural factors. Five studies used the PSS translated into different languages but only one study validated the translated version. Six studies reported the reliability of the PSS. The PSS-14 and PSS-10 may be appropriately used in immigrants to measure psychological stress.ConclusionsSome issues, such as the PSS’s reliability and validity, need to be addressed in future use in immigrants.

Here, we show that hypoxia drives especially long-lasting epithelial-mesenchymal transition (EMT) in pancreatic ductal adenocarcinoma (PDAC) primarily through a positive-feedback histone methylation-MAPK signaling axis. We find that neoplastic PDAC cells preferentially undergo EMT in hypoxic tumor regions in multiple model systems and that hypoxia drives a cell-autonomous EMT in PDAC cells which, unlike EMT in response to growth factors, can last for weeks. We further demonstrate that hypoxia reduces histone demethylase KDM2A activity, suppresses PP2 family phosphatase expression, and activates MAPKs to post-translationally stabilize histone methyltransferase NSD2, leading to an H3K36me2-dependent EMT in which hypoxia-inducible factors play only a supporting role. This mechanism can be antagonizedin vivoby combinations of MAPK inhibitors that may be effective in multi-drug therapies designed to target EMT.

Purpose: The purpose of the study was to examine the factors associated with diabetes self-care behaviors (DSCB) in people with visual impairment (PVI), including demographics, disease-related characteristics, and psychosocial factors (self-efficacy, depression, and family support). Methods: A descriptive cross-sectional study was conducted. Adults with visual impairment and diabetes were recruited online and through posting notices, and a total of 141 participants were included. Measurements were completed using email and telephone surveys. Multiple linear regression analysis was performed to examine the factors associated with DSCB. Results: Higher self-efficacy and positive family support were significant predictors of better DSCB, whereas higher negative family support was a significant predictor of worse DSCB. Diabetes medication regimen was another major influencing factor on DSCB. However, depression was not associated with DSCB. Conclusion: Diabetes interventions for the visually impaired should have strategies to improve vulnerable areas of diabetes self-care, such as blood glucose monitoring. Health care providers are needed to consider diabetes education programs focused on improving self-efficacy or include family members in interventions to promote DSCB in PVI. Further studies are required to understand the problems and solutions for diabetes self-care in this population.

Background: Prognosis of patients with HER-2 positive metastatic breast cancer (MBC) has been revolutionized with the development of dual antibodies targeting HER-2 and antibody-drug conjugate, but resistance to anti-HER-2 therapy is inevitable ultimately. PI3K-AKT-mTOR pathway aberration is known to be one of the resistance mechanisms. This randomized phase 2 pilot study evaluated safety and efficacy of Herzuma® (trastuzumab biosimilar) plus Gedatolisib (dual PI3K/mTORC inhibitor) in patients with HER-2 positive MBC who progressed after multiple lines of therapy. Methods: Patients with HER-2 positive MBC with known PIK3CA pathologic mutation or amplification whose disease progressed after more than two HER-2 directed therapy were enrolled in the study. They received Herzuma® (8mg/kg IV for 1st cycle loading dose, and then 6mg/kg IV every 3 weeks) plus Gedatolisib (180mg on D1, 8, 15 of every 21 days). We evaluated efficacy of the combination treatment as interim analysis. The data cutoff of this interim analysis was Aug 4, 2020. Results: As a pilot study, 15 patients were enrolled and followed for a median of 2.3 months. At data cutoff, 11 patients were eligible for response assessment. All patients were confirmed to have pathologic PIK3CA aberrations: H1047R, H1047L, E542Q, E542K, E453K, N345K, and PIK3CA amplification. Five patients reached partial response (PR) as their best response, three were stable disease (SD), and three had progressive disease (PD). All patients who have reached PR remain on investigational treatment at the data cutoff point, and the longest one is on treatment for 7.8 months. One of the SD patients ended treatment due to disease progression, and the other two have been undergoing treatment. Overall, response rate was 45.5% and disease control rate was 72.7%. No fatal adverse events related to trial medication were reported. Conclusion: In this phase 2 pilot study, Trastuzumab biosimilar plus Gedatolisib presented 45.5% of response rate with manageable toxicity in patients with HER-2 positive MBC with PIK3CA aberration. Clinical trial information: NCT03698383 Acknowledgement: this research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health &Welfare, Republic of Korea (Grant number: HI17C2206). Citation Format: Ju Won Kim, Hee Kyung Ahn, Jong Gwon Choi, Yee Soo Chae, Gyeong Won Lee, Keon Uk Park, Eun Mi Lee, Sung Hoon Sim, Jee Hyun Kim, Yeon Hee Park, Mi So Kim, Jin Hyun Park, Jeong Eun Kim, Han Jo Kim, Mi Sun Ahn, So Yeon Oh, Min Hwan Kim, Su-Jin Koh, Kyoung Eun Lee, Myoung Joo Kang, Jae Ho Byun, Joo young Ha, Jung Hye Kwon, Joo Young Jung, Su Ee Lee, In Hae Park, Kyong Hwa Park. Phase II pilot study of trastuzumab biosimilar (herzuma®) plus gedatolisib in patients with HER-2 positive metastatic breast cancer who progressed after 2 or more HER-2 directed chemotherapy [KM-10A/KCSG18-13 interim analysis] [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-39.

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.

Chemical treatments of toxic cyanide (CN–) typically involve its conversion to cyanate (OCN–), which is less toxic. An ideal treatment should be its conversion to N2 and CO2. This study proposed an...

Background By investigating treatment patterns and outcomes in locally advanced head and neck squamous cell carcinoma (LA-HNSCC), we aimed at providing valuable insights into the optimal therapeutic strategy for physicians in real-world practice. Methods This is a multi-institutional study enrolled the patients with stage III to IVB LA-HNSCC, except for nasopharyngeal carcinoma, from 2004 to 2015 in thirteen referral hospitals capable of multidisciplinary care. Results A total of 445 LA-HNSCC patients were analyzed. The median age was 61 years (range, 24–89). The primary tumor location was the oropharynx in 191 (43%), oral cavity in 106 (24%), hypopharynx in 64 (14%), larynx in 57 (13%) and other sites in 27 (6%). The most common stage was T2 in 172 (39%), and N2 in 245 (55%). Based on treatment intents, 229 (52%) of the patients received definitive concurrent chemoradiotherapy (CCRT) and 187 (42%) underwent surgery. Approximately 158 (36%) of the study population received induction chemotherapy (IC). Taken together, 385 (87%) of the patients underwent combined therapeutic modalities. The regimen for definitive CCRT was weekly cisplatin in 58%, 3-weekly cisplatin in 28% and cetuximab in 3%. The preferred regimen for IC was docetaxel with cisplatin in 49%, and docetaxel, cisplatin plus fluorouracil in 27%. With a median follow-up of 39 months, one-year and two-year survival rates were 89 and 80%, respectively. Overall survival was not significantly different between CCRT and surgery group (p = 0.620). Conclusions In patients with LA-HNSCC, the majority of patients received combined therapeutic modalities. Definitive CCRT, IC then definitive CCRT, and surgery followed by adjuvant CCRT or radiotherapy are the preferred multidisciplinary strategies in real-world practice.

Government healthcare expenditure is rising in Korea, and the costs incurred by patients in Korea exceed those incurred by patients in other Organization for Economic Co-operation and Development countries. Despite the increasing health expenditure, patient demand for services is increasing as well, so it is now becoming recognized that cancer care needs to be balanced. The most important measure in cancer care optimization is to provide high-quality care while keeping costs sustainable. The Korean Cancer Association considers the current situation of cancer therapy in Korea the foremost issue, which has led to the implementation of the nationwide ‘Right Decisions in Cancer Care’ initiative. This initiative is based on the concepts of medical professionalism in that it should be led by physicians working in the field of oncology, that education should be offered to patients and clinicians, and that it should influence healthcare policy. In this article, we introduce the nationwide ‘Right Decision in Cancer Care’ initiative and highlight the five initial items on its agenda. The agenda is open to expansion and update as the medical environment evolves and additional clinical evidence becomes available.

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.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.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.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.

Objective The aim of this study was to estimate the prevalence of major psychiatric disorders among North Korean defectors (NKD) settled in South Korea.Methods The study population consisted of 294 North Korean defectors, aged 18 to 64 years settled in South Korea for 3 years or less. Between June 1, 2016 and October 31, 2016, face-to-face interviews were conducted using the North Korean version of the WHO-Composite International Diagnostic Interview (NK-CIDI) to diagnose DSM-IV psychiatric disorders.Results The lifetime prevalence of any DSM-IV psychiatric disorders was 62.2% in NKD and 25.0% in the general Korean population. The prevalence of specific disorders in NKD and general Korean population was as follows: 22.3% and 4.9% for major depressive disorder (MDD), 12.2% and 1.4% for post-traumatic stress disorder (PTSD), 18.0% and 4.8% for nicotine dependence, and 14.5% and 11.2% for alcohol abuse. The incidence of every single psychiatric disorder varied in each country. For instance, the generalized anxiety disorder, specific phobia, and alcohol use disorder occurred more frequently in North Korea whereas PTSD was more prevalent in other countries.Conclusion The prevalence of psychiatric disorders among NKD was quite higher than in the general population of South Korea.

We look at the population dynamics of an ecological system considering the Allee effect across different levels of population growth rates. The model is described by the growth and degradation of population size by multiplying a threshold term by the Allee effect. When the population of a species is low, the population of the system is not maintained and collapses to extinction. A wide survival region is observed in the dynamics of the Allee effect, and we report a bifurcation diagram for selected control parameters. We identify the chaotic region based on Lyapunov exponents. We obtain a phase diagram distinguishing extinction, periodic oscillation, the chaotic region, and the unstable region in the control parameter space. We observe two sets of chaotic bands one for low and the other for high values of the Allee effect. The Allee effect diversifies the dynamic region in parameter space.

The objective of this study was to prioritize the most burdensome menopause symptoms among Cambodian women utilizing the best-worst scale (BWS). In total, 180 women aged 40-60 who lived in a community setting were recruited from four regions of Cambodia via convenience sampling. Using the BWS, 12 choice sets were prepared by combining 11 symptoms from the menopause rating scale (MRS), and the BWS choice sets were generated with the orthogonal main effects design (OMED). Counting approach determined the women's health priorities and calculated the best-minus-worst (BW) score. The modeling approach measured each respondent's basic utility function. Of the 180 participants, 41.1% were between the ages of 40 and 49, and 25.0% were over 50. The counting and modeling approaches revealed that heart discomfort was the most burdensome symptom (coefficient 0.739, p .001) followed by joint and muscular discomfort (coefficient 0.606, p .001) and sleep problems (coefficient 0.507, p .001), whereas vaginal dryness was the least burdensome symptoms (coefficient -0.164, p = .018). This study revealed that the most burdensome menopause symptom among Cambodian women was heart discomfort while vaginal dryness was the least burdensome. The BWS enabled to prioritize the burdensome menopausal symptoms which warrants future studies using the BWS.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extensive fibroinflammatory stroma and often experiences conditions of insufficient oxygen availability, or hypoxia. Cancer-associated fibroblasts (CAF) are a predominant and heterogeneous population of stromal cells within the pancreatic tumor microenvironment. Here, we uncover a previously unrecognized role for hypoxia in driving an inflammatory phenotype in PDAC CAFs. We identify hypoxia as a strong inducer of tumor IL1α expression, which is required for inflammatory CAF (iCAF) formation. Notably, iCAFs preferentially reside in hypoxic regions of PDAC. Our data implicate hypoxia as a critical regulator of CAF heterogeneity in PDAC.

Backgrounds Since OlympiAD study, National Comprehensive Cancer Network guideline recommends assessment of germline BRCA1/2 mutation in all patients with recurrent or metastatic breast cancer to identify candidates for PARP inhibitor therapy, which is not always possible in clinical practice due to limited resources for testing. Data on the prevalence of gBRCA mutation is still lacking, especially in patients with non-high risk for hereditary breast and ovarian cancer syndrome. In this study, we investigated prevalence of gBRCA mutation in unselected Korean patients with HER2-negative advanced BC in a prospective cohort and analyzed oncologic outcome. Methods Eligible patients were diagnosed with HER2-negative advanced BC and had initiated palliative systemic treatment. Peripheral blood was prospectively drawn from each patient and gBRCA mutation status was assessed by next generation sequencing using NGeneBio BRCAaccuTest®. In 100 patients, somatic mutations including BRCA1/2 from tumor tissue were investigated using targeted panel sequencing. To estimate the prevalence of gBRCA mutation with margin of error to be no more than ±4% at the 95% confidence interval in a population size of 20,000, 583 patients were to be enrolled. Results A total of 583 patients were enrolled between Oct 2019 and Mar 2022, and the prevalence of gBRCA mutation was analyzed in 570 patients, excluding ineligible patients. Median age was 54 years old (range 26-87) and 567 patients were female. 475 patients had HR+/HER2- BC and 94 patients had triple negative breast cancer (TNBC). The overall prevalence of gBRCA1/2 pathogenic mutation was 7.3% (42/570) in unselected patients. The prevalence of gBRCA1 mutation was 1.6%(9/570) overall, 0.8%(4/475) in HR+/HER2- BC, and 5.3%(5/94) in TNBC. The prevalence of gBRCA2 mutation was 5.8%(33/570) overall, 6.3%(30/475) in HR+/HER2- BC, 3.2%(3/94) in TNBC. Prevalence in low risk TNBC (>60 years at first BC diagnosis, no known family history of relevant cancer and unilateral breast cancer) was 10.5% (2/19, all 2 patients had gBRCA2 mutation). Prevalence in low risk HR+/HER2- (>40 years at first BC diagnosis, no known family history of relevant cancer and unilateral breast cancer) was 5.9% (18/307, 17 patients had gBRCA2 mutation). The overall prevalence of gBRCA1/2 pathogenic mutation in Korean patients with low risk HER2-negative advanced BC was 6.1%. The result of somatic mutation, treatment patterns and clinical outcome according to gBRCA1/2 mutation will be further analyzed. Conclusions The prevalence of gBRCA mutation among Korean patients with HER2-negative advanced BC classified as low risk (6.1%) in this study supports routine testing of gBRCA mutation in this population. Citation Format: Hee Kyung Ahn, Jee Hung Kim, Mirae Kim, Seri Park, Su-Jin Koh, Joo Hyuk Sohn, Myoung Joo Kang, Kyung Hae Jung, Kyoung Eun Lee, Jieun Lee, Sung Ae Koh, Yee Soo Chae, Jae Ho Byun, In Hae Park, Hee-Jun Kim, Jee Hyun Kim, Han Jo Kim, Joo Young Jung, Jung Lim Lee, Yoon Young Cho, Kyong Hwa Park, Ji-Yeon Kim, Seock-Ah Im, Yeon Hee Park. Prevalence of germline BRCA mutations in unselected Korean patients with HER2-negative breast cancer: A Prospective cohort study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-03-14.

The current study examined characteristics of early-onset and late-onset disability in older adults and identified predictors of health-related quality of life (HRQoL). This is a secondary data analysis of the 2017 national survey in South Korea. Participants were 4,014 older adults with disabilities, who were divided into an early-onset group ( n = 2,229) and late-onset group ( n = 1,785). Data were analyzed using complex sample analyses. Difficulties during outdoor activity and transportation use, self-rated health, and stress were common predictors in both groups. Comorbidity was a significant predictor only in the early-onset group. Use of information technology devices, household income, and perceived social discrimination were significant predictors in the late-onset group. Characteristics and predictors of HRQoL were different between groups, despite sharing common characteristics. It is necessary to improve support systems and health care services for older adults with disabilities. [ Journal of Gerontological Nursing, 48 (3), 37–47.]

Background: Chemoresistance is a major problem in gastric cancer (GC) management with an unknown underlying mechanism. In this study, we aimed to establish a 5-fluorouracil (5-FU)-resistant GC cell line and explore the biological characteristics related to its chemoresistance.Materials and Results: The chemotherapeutic agent-resistant GC cell line (AGS-R) was established by continuous exposure of AGS cells to 5-FU. These cells showed morphologic changes and increased level of thymidylate synthase (TS) mRNA compared with the parental cells. AGS-R also showed down-regulation of β-catenin activity with decreased migration and invasion. The expression of CD44 was increased in AGS-R cells and this was reversed with the inhibition of Notch1.Conclusions: 5-FU resistant gastric cancer cell line was well established and these cells showed increased stemness which was reversed with Notch1 inhibition.

Purpose The treatment of male breast cancer (MBC) has been extrapolated from female breast cancer (FBC) because of its rarity despite their different clinicopathologic characteristics. We aimed to investigate the distribution of intrinsic subtypes based on immunohistochemistry, their clinical impact, and treatment pattern in clinical practice through a multicenter study in Korea.Materials and Methods We retrospectively analyzed clinical data of 248 MBC patients from 18 institutions across the country from January 1995 to July 2016.Results The median age of MBC patients was 63 years (range, 25 to 102 years). Among 148 intrinsic subtype classified patients, 61 (41.2%), 44 (29.7%), 29 (19.5%), and 14 (9.5%) were luminal A, luminal B, human epidermal growth factor receptor 2, and triple-negative breast cancer, respectively. Luminal A subtype showed trends for superior survival compared to other subtypes. Most hormone receptor-positive patients (166 patients, 82.6%) received adjuvant endocrine treatment. Five-year completion of adjuvant endocrine treatment was associated with superior disease-free survival (DFS) in patients classified with an intrinsic subtype (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04 to 0.49; p=0.002) and in all patients (HR, 0.16; 95% CI, 0.05 to 0.54; p=0.003).Conclusion Distribution of subtypes of MBC was similar to FBC and luminal type A was most common. Overall survival tended to be improved for luminal A subtype, although there was no statistical significance. Completion of adjuvant endocrine treatment was associated with prolonged DFS in intrinsic subtype classified patients. MBC patients tended to receive less treatment. MBC patients should receive standard treatment according to guidelines as FBC patients.

Investigation of responsiveness-associated genes using longitudinal mutation analyses after standard treatments in recurrent gastric cancer (GC) is limited.To evaluate the somatic mutations associated with resistance to combined treatment involving fluorouracil (FU) or platinum (PL) in advanced GC.Samples from patients with advanced GC treated with FU or PL alone, or surgery plus FU/PL, were studied. GC patients who relapsed after standard chemotherapy (FU/PL) and with presence of tumor samples from initial diagnosis and recurrence were included. Targeted sequencing analysis of 143 cancer-related genes was performed using an Oncomine Comprehensive Cancer Panel.Matched samples of primary and recurrent lesions were analyzed in sixteen patients with GC. When genes with recurrent mutations in two or more patients were used as specific findings, a total of 26 genes were found. TP53 was the most predominantly increased allele frequency (AF) in recurrent GCs after standard treatment. The mutational AF of ERBB2, PTEN, and BRCA2 also commonly increased, suggesting the role of these mutations in treatment resistance, whereas the mutational AF of VLH, NF1, and STK11 frequently decreased in recurrent tumors, suggesting the role of these mutations in increasing sensitivity to treatment. TCGA gastric cancer data (n = 436) were analyzed, and mutation sites detected in 16 GC patients in this study were in agreement with TCGA cohort with some exceptions. Overall survival according to gene expression associated with chemotherapy responsiveness exhibited compatible patterns with gain or loss-of-function mutations of each gene.Mutations in TP53, ERBB2, PTEN, BRCA2, VHL, NF1, and STK11 are candidate somatic alterations related to chemoresistance in GC.

Xanthogranulomatous inflammation is a rare inflammatory reaction, characterized by lipid-laden macrophages, known as xanthomas, in histopathologic examination. Aggressive xanthogranulomatous inflammation often manifests as local infiltration but does not affect distant organs unless combined with rare systemic diseases. We report a case of focal xanthogranulomatous pyelonephritis (XGP) associated with severe xanthogranulomatous cholecystitis. Focal XGP was suspected in radiologic examination that showed a cystic lesion with an infiltrative margin, which were surgically resected and confirmed in pathologic examination. To our knowledge, this is the first report of focal xanthogranulomatous pyelonephritis associated with xanthogranulomatous cholecystitis. Moreover, we found peripheral hypointensity around the cystic lesion in the T2-weighted image, probably reflecting hemorrhage and fibrosis of the xanthogranulomatous inflammation.