Long Term Psychiatric and Endocrine Complications Following Hematopoietic Stem Cell Transplantation in Hematologic Disease in Korea: A Nation-wide Cohort Study.

Purpose: Numerous patients experience long-term complications after HSCT. This study aimed to identify the frequency and risk factors for psychiatric and endocrine complications following HSCT through big data analyses. Materials and Methods: We established a cohort of patients with hematologic disease who underwent HSCT in Korea between 2010 and 2012 using the Health Insurance Review & Assessment Service data. A total of 3,636 patients were identified, and insurance claims were tracked using psychiatric and endocrine diagnostic International Classification of Diseases-10th Revision codes for the ensuing decade. We identified the incidence rates of long-term complications based on the baseline disease and HSCT type. Prognostic factors for each complication were scrutinized using logistic regression analysis. Results: A total of 1,879 patients underwent allogeneic HSCT and 1,757 patients received autologous HSCT. Post-HSCT, 506 patients were diagnosed with depression, 465 with anxiety disorders, and 659 with diabetes. The highest incidence of long-term complications occurred within the first year post-HSCT (12.2%), subsequently decreasing over time. Risk factors for depressive disorders after allogeneic HSCT included female sex, a total body irradiation based conditioning regimen, and cyclosporine. Identified risk factors for diabetes mellitus comprised old age, TBI-based conditioning regimen, and non-Antithymocyte globulin protocol. Regarding autologous HSCT, only female sex was identified as a risk factor for depressive disorders, whereas elderly patients and those with multiple myeloma were identified as poor prognostic factors for diabetes mellitus. Conclusion: The incidence of long-term psychiatric and endocrine complications post-HSCT remains high, and patients with risk factors for these complications require vigilant follow-up.

Analysis of Response and Progression Patterns of Tyrosine Kinase Inhibitors in Recurrent or Metastatic Adenoid Cystic Carcinoma: A Post Hoc Analysis of Two KCSG Phase II Trials.

Purpose: In this study, we evaluated 66 patients diagnosed with adenoid cystic carcinoma (ACC) enrolled in two Korean Cancer Study Group trials to investigate the response and progression patterns in recurrent and/or metastatic ACC treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs). Materials and Methods: We evaluated 66 patients diagnosed with ACC who were enrolled in the Korean Cancer Study Group trials. The tumor measurements, clinical data, treatment outcomes, and progression patterns of therapy were analyzed. Results: In the 66 patients (53 receiving axitinib and 13 receiving nintedanib), the disease control rate was 61%, and 3 patients achieved partial response. The median follow-up, median progression-free survival (PFS), overall survival, and 6-month PFS rate were 27.6, 12.4, and 18.1 months and 62.1%, respectively. Among 42 patients who experienced progression, 27 (64.3%) showed target lesion progression. Bone metastasis was an independent poor prognostic factor. Conclusion: Overall, most patients demonstrated stable disease with prolonged PFS; however, prominent target lesion progression occurred in some patients. Thus, PFS may capture VEGFR-TKI efficacy better than the objective response rate.

Phase II study of nivolumab in patients with genetic alterations in DNA damage repair and response who progressed after standard treatment for metastatic solid cancers (KM-06).

BACKGROUND: Immune-modulating antibodies targeting programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) have demonstrated promising antitumor efficacy in various types of cancers, especially highly mutated ones. Genetic alterations in DNA damage response and repair (DDR) genes can lead to genetic instability, often accompanied by a high tumor mutation burden (TMB). However, few studies have validated the aberration of DDR genes as a predictive biomarker for response to immune-modulating antibodies. METHODS: The KM-06 open-label, multicenter, single-arm, phase II trial evaluated the safety and efficacy of nivolumab in refractory solid cancers with DDR gene mutations assessed by clinically targeted sequencing. Nivolumab (3 mg/kg) was administered every 2 weeks until disease progression, unacceptable toxicity, or for 24 months. The primary endpoint was the objective response rate (ORR) as per RECIST V.1.1 criteria. RESULTS: A total of 48 patients were enrolled in the study (median age 61, 58.3% male). The most common cancer type was colorectal cancer (41.7%), followed by prostate and biliary tract cancer (8.3% each). Eight patients achieved a partial response as their best overall response, resulting in an ORR of 17.8%. The disease control rate was 60.0%. The median progression-free survival was 2.9 months. Treatment-related adverse events of any grade and grade ≥3 occurred in 44 (91.7%) and 4 (8.3%) patients, respectively. Clinically targeted sequencing data inferred both TMB and microsatellite instability (MSI). Using a TMB cut-off of 12 mut/Mb, there were significant differences in overall survival (p=0.00035), progression-free survival (p=0.0061), and the best overall response (p=0.05). In the RNA sequencing analysis, nivolumab responders showed activation of the interleukin signaling pathway. Patients who experienced early progression presented high epithelial-mesenchymal transition signaling pathway activation. The responders exhibited a marked increase in PD-1-/Ki67+CD8 T cells at the early stage of treatment (C3D1) compared with non-responders (p=0.03). CONCLUSIONS: In this phase II trial, nivolumab demonstrated moderate efficacy and manageable toxicity in patients with solid cancer harboring DDR gene mutations. A high TMB (>12 mut/Mb) and MSI score (>2.5) determined through clinically target sequencing presented significant discriminatory power for the nivolumab response. TRIAL REGISTRATION NUMBER: NCT04761744.

Impact of PIK3CA and cell cycle pathway genetic alterations on durvalumab efficacy in patients with head and neck squamous cell carcinoma: Post hoc analysis of TRIUMPH study.

OBJECTIVES: This study aimed to investigate whether genetic alterations in PI3KCA and the cell cycle pathways influence the efficacy of durvalumab, an immune checkpoint inhibitor, in patients with head and neck squamous cell carcinoma (HNSCC) who had previously failed platinum-based treatment. MATERIALS AND METHODS: We obtained data from a phase II umbrella trial of patients with HNSCC who failed platinum-based treatment (TRIUMPH, NCT03292250). Patients receiving durvalumab treatment comprised those with PIK3CA alterations (Group A), those with cell cycle pathway alterations such as CDKN2A (Group B), and those with no druggable genetic alterations (Group C). We analyzed the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in each group and evaluated the potential predictive factors for durvalumab. RESULTS: We analyzed the data of 87 patients: 18, 12, and 57 in groups A, B, and C, respectively. The ORRs were 27.8 %, 8.3 %, and 15.8 % in Groups A, B, and C, respectively (P = 0.329), and the median PFS for each group was 2.3, 1.6, and 1.7 months, respectively, with no significant differences between the groups (P = 0.24). Notably, patients with lower neutrophil-lymphocyte ratio (NLR) (≤5.8) had longer PFS (median, 2.8 vs 1.6 months, P < 0.001), while those with lower platelet-lymphocyte ratio (PLR) (≤491.2) exhibited longer PFS (median, 1.8 vs 1.2 months, P < 0.001). CONCLUSION: Durvalumab's efficacy was similar, irrespective of the presence of PIK3CA or cell cycle pathway genetic alterations in patients with platinum-resistant HNSCC. The NLR and PLR may be promising predictive biomarkers.

N-Iminopyridinium Compounds in Giese Reaction: Photoinduced Homolytic N-N and C-C Bond Cleavage for Cyanoalkyl Radical Generation.

We present an innovative photoinduced cyanoalkyl radical addition methodology using N-iminopyridinium reagents derived from cyclic ketones. Mechanistic investigations reveal the association of the excited Hantzsch ester and iminopyridinium with pyridyl radical generation. The ensuing cascade involving homolytic N-N bond and C-C bond cleavage of the pyridyl radical ultimately leads to the formation of cyanoalkyl radical species, leading to diverse Giese-type products. The method showcases versatility and synthetic utility in late-stage functionalization.

Biomass- and Carbon Dioxide-Derived Polyurethane Networks for Thermal Interface Material Applications.

Recent environmental concerns have increased demand for renewable polymers and sustainable green resource usage, such as biomass-derived components and carbon dioxide (CO2). Herein, we present crosslinked polyurethanes (CPUs) fabricated from CO2- and biomass-derived monomers via a facile solvent-free ball milling process. Furan-containing bis(cyclic carbonate)s were synthesized through CO2 fixation and further transformed to tetraols, denoted FCTs, by aminolysis and utilized in CPU synthesis. Highly dispersed polyurethane-based hybrid composites (CPU-Ag) were also manufactured using a similar ball milling process. Due to the malleability of the CPU matrix, enabled by transcarbamoylation (dynamic covalent chemistry), CPU-based composites are expected to present very low interfacial thermal resistance between the heat sink and heat source. The characteristics of the dynamic covalent bond (i.e., urethane exchange reaction) were confirmed by the results of dynamic mechanical thermal analysis and stress relaxation analysis. Importantly, the high thermal conductivity of the CPU-based hybrid material was confirmed using laser flash analysis (up to 51.1 W/m·K). Our mechanochemical approach enables the facile preparation of sustainable polymers and hybrid composites for functional application.

Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non-Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04).

PURPOSE: In the treatment of non-small-cell lung cancer (NSCLC) with a driver mutation, the role of anti-PD-(L)1 antibody after tyrosine kinase inhibitor (TKI) remains unclear. This randomized, open-label, multicenter, phase III study evaluates the efficacy of atezolizumab plus bevacizumab, paclitaxel, and carboplatin (ABCP ) in EGFR- or ALK-mutated NSCLC that progressed before TKI therapy. MATERIALS AND METHODS: We compared the clinical efficacy of ABCP followed by maintenance therapy with atezolizumab plus bevacizumab with pemetrexed plus carboplatin or cisplatin (PC) followed by pemetrexed maintenance. The primary end point was progression-free survival (PFS). RESULTS: A total of 228 patients with activating EGFR mutation (n = 215) or ALK translocation (n = 13) were enrolled from 16 sites in the Republic of Korea and randomly assigned at 2:1 ratio to either ABCP (n = 154) or PC arm (n = 74). The median follow-up duration was 26.1 months (95% CI, 24.7 to 28.2). Objective response rates (69.5% v 41.9%, P < .001) and median PFS (8.48 v 5.62 months, hazard ratio [HR], 0.62 [95% CI, 0.45 to 0.86]; P = .004) were significantly better in the ABCP than PC arm. PFS benefit increased as PD-L1 expression increased, with an HR of 0.47, 0.41, and 0.24 for PD-L1 ≥1%, ≥10%, and ≥50%, respectively. Overall survival was similar between ABCP and PC arm (20.63 v 20.27 months, HR, 1.01 [95% CI, 0.69 to 1.46]; P = .975). The safety profile of the ABCP arm was comparable with that previously reported, with no additional safety signals, but higher rates of treatment-related adverse events were observed compared with the PC arm. CONCLUSION: To our knowledge, this study is the first randomized phase III study to demonstrate the clinical benefit of anti-PD-L1 antibody in combination with bevacizumab and chemotherapy in patients with EGFR- or ALK-mutated NSCLC who have progressed on relevant targeted therapy.

Catechol-Amyloid Interactions.

This review introduces multifaceted mutual interactions between molecules containing a catechol moiety and aggregation-prone proteins. The complex relationships between these two molecular species have previously been elucidated primarily in a unidirectional manner, as demonstrated in cases involving the development of catechol-based inhibitors for amyloid aggregation and the elucidation of the role of functional amyloid fibers in melanin biosynthesis. This review aims to consolidate scattered clues pertaining to catechol-based amyloid inhibitors, functional amyloid scaffold of melanin biosynthesis, and chemically designed peptide fibers for providing chemical insights into the role of the local three-dimensional orientation of functional groups in manifesting such interactions. These orientations may play crucial, yet undiscovered, roles in various supramolecular structures.

Fe-Catalyzed C-H Alkenylation of Dialkyl Anilines with Disulfonylethenes.

The oxidative alkenylation reaction of α-aminoalkyl C(sp3)-H bonds has been investigated with (E)-1,2-bis(sulfonyl)ethenes. The catalytic process of iron-polypyridyl complexes drives the single-electron oxidation of dialkyl anilines, resulting in the formation of α-aminoalkyl radical species. Subsequent cascades of radical addition and elimination reactions ensue, ultimately leading to the generation of sulfonylated allylic amine products. The utility of these products extends further, enabling the synthesis of multisubstituted heterocycles like pyrroles, pyrazines, and triazoles.

Artificial intelligence-powered spatial analysis of tumor-infiltrating lymphocytes as a predictive biomarker for axitinib in adenoid cystic carcinoma.

BACKGROUND: This study analyzed the predictive value of artificial intelligence (AI)-powered tumor-infiltrating lymphocyte (TIL) analysis in recurrent or metastatic (R/M) adenoid cystic carcinoma (ACC) treated with axitinib. METHODS: Patients from a multicenter, prospective phase II trial evaluating axitinib efficacy in R/M ACC were included in this study. H&E whole-side images of archival tumor tissues were analyzed by Lunit SCOPE IO, an AI-powered spatial TIL analyzer. RESULTS: Twenty-seven patients were included in the analysis. The best response was stable disease, and the median progression-free survival (PFS) was 11.1 months (95% CI, 9.2-13.7 months). Median TIL densities in the cancer and surrounding stroma were 25.8/mm2 (IQR, 8.3-73.0) and 180.4/mm2 (IQR, 69.6-342.8), respectively. Patients with stromal TIL density >342.5/mm2 exhibited longer PFS (p = 0.012). CONCLUSIONS: Cancer and stromal area TIL infiltration were generally low in R/M ACC. Higher stromal TIL infiltration was associated with a longer PFS with axitinib treatment.

Integrative analysis of risk factors for immune-related adverse events of checkpoint blockade therapy in cancer.

Immune-related adverse events (irAEs) induced by checkpoint inhibitors involve a multitude of different risk factors. Here, to interrogate the multifaceted underlying mechanisms, we compiled germline exomes and blood transcriptomes with clinical data, before and after checkpoint inhibitor treatment, from 672 patients with cancer. Overall, irAE samples showed a substantially lower contribution of neutrophils in terms of baseline and on-therapy cell counts and gene expression markers related to neutrophil function. Allelic variation of HLA-B correlated with overall irAE risk. Analysis of germline coding variants identified a nonsense mutation in an immunoglobulin superfamily protein, TMEM162. In our cohort and the Cancer Genome Atlas (TCGA) data, TMEM162 alteration was associated with higher peripheral and tumor-infiltrating B cell counts and suppression of regulatory T cells in response to therapy. We developed machine learning models for irAE prediction, validated using additional data from 169 patients. Our results provide valuable insights into risk factors of irAE and their clinical utility.

Treatment outcomes of advanced/metastatic extramammary Paget's disease in Korean patients: KCSG-RC20-06.

BACKGROUND: Extramammary Paget's disease (EMPD) is rare. There are no standard treatments due to its rarity and few clinical trials. METHODS: The objective of this multicenter study was to investigate treatment outcomes of Korean patients with advanced/metastatic EMPD. Data were collected retrospectively from 14 institutions participating in Korean Cancer Study Group (KCSG) Rare Cancer Committee. RESULTS: A total of 37 patients were identified. Of these 37 patients, 6 received locoregional therapy as a first-line treatment. In 31 patients who received systemic chemotherapy as a first-line treatment, platinum-based chemotherapy (n = 22) achieved an objective response rate (ORR) of 45.5% and a median progression-free survival (PFS) of 7.89 months. Taxane-based chemotherapy (n = 8) achieved an objective response rate of 62.5% and median PFS of 9.73 months. In second-line chemotherapy, platinum-based chemotherapy (n = 4) had a disease control rate (DCR) of 75.0% and median PFS of 3.45 months. Taxane-based chemotherapy (n = 8) had a DCR of 75.0% and a median PFS of 8.67 months. Six patients received anti-human epidermal growth factor receptor 2 (HER2) antibody during first- and second-line chemotherapy. Overall, systemic chemotherapy combined with anti-HER2 antibody had an ORR of 100% and a median PFS of 13.31 months. The ORR and PFS with systemic chemotherapy combined with trastuzumab was better than platinum- and taxane-based chemotherapy only. CONCLUSIONS: Due to its rarity, advanced or metastatic EMPD still has no established standard treatment. Results of our study indicate that the combination of trastuzumab with taxane has longer survival than trastuzumab monotherapy or conventional platinum- or taxane-based chemotherapy.

Associations between missing teeth and the risk of cancer in Korea: a nationwide cohort study.

BACKGROUND: Poor dental health is correlated with an increased risk of cancer. Using a nationwide population cohort database, we investigated which cancer is highly associated with poor dental health and which dental indicator mostly influences cancer risk. METHODS: This study was conducted using the National Health Checkups (NHC) and National Health Insurance System (NHIS) database in Korea. NHC in Korea includes dental examinations. We retrieved subjects who underwent NHC between 2002 and 2003 and their medical information in NHIS database was followed until December 31,2015. RESULTS: Data for 200,170 who participated in the NHC between 2002 and 2003 were analysed. During the maximum follow-up period of 13 years, 15,506 (7.75%) subjects were diagnosed with cancer. The median time to cancer diagnosis after the dental examination was 87 months (range, 51-119 months). The proportion of people with missing teeth was higher in the cancer-diagnosed group than in the non-diagnosed group (26.27% vs. 22.59%, p < 0.001). Among several dental health factors, missing teeth were significantly associated with higher cancer risk. Subjects with missing teeth showed a 12% increased cancer risk compared to those without missing teeth (odds ratio [OR] 1.12, 95% confidence interval [CI], 1.08-1.16). The risk was significantly higher, especially in lung, head and neck, pancreatic, liver, biliary, and esophageal cancers (OR 1.27 [95% CI, 1.14-1.41], 1.32 [95% CI, 1.13-1.55], 1.27 [95% CI, 1.02-1.58], 1.24 [95% CI, 1.1-1.4], 1.28 [95% CI, 1.03-1.6], 1.4 [95% CI, 1.04-1.88], respectively). CONCLUSIONS: Missing teeth were the most important dental indicator associated with cancer risk. Korean adults with missing teeth should be cautious about the risk of several cancers, particularly head and neck, lung, gastrointestinal, hepatobiliary, and pancreatic cancer.

A phase 2 multicenter study of docetaxel-PM and trastuzumab-pkrb combination therapy in recurrent or metastatic salivary gland carcinomas.

BACKGROUND: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. The high positivity rate for human epidermal growth factor receptor 2 (HER2) led to an investigation of the efficacy of HER2-targeted agents. Docetaxel-PM (polymeric micelle) is a low-molecular-weight, nontoxic, biodegradable, and docetaxel-loaded micellar formulation. Trastuzumab-pkrb is a biosimilar to trastuzumab. METHODS: This was a multicenter, single-arm, open-label phase 2 study. Patients with HER2-positive (immunohistochemistry [IHC] score of ≥2+ and/or HER2/chromosome enumeration probe 17 [CEP17] ratio of ≥2.0) advanced SDCs were enrolled. Patients received docetaxel-PM (75 mg/m2 ) and trastuzumab-pkrb (8 mg/kg in the first cycle and 6 mg/kg in subsequent cycles) every 3 weeks. Primary end point was objective response rate (ORR). RESULTS: A total of 43 patients were enrolled. The best objective responses were partial response in 30 (69.8%) patients and stable disease in 10 (23.3%) patients, leading to an ORR of 69.8% (95% confidence interval [CI], 53.9-82.8) and a disease control rate of 93.0% (80.9-98.5). Median progression-free survival, duration of response, and overall survival were 7.9 (6.3-9.5), 6.7 (5.1-8.4), and 23.3 (19.9-26.7) months, respectively. Patients with HER2 IHC score of 3+ or HER2/CEP17 ratio ≥2.0 demonstrated better efficacies compared to those with HER2 IHC score of 2+. Thirty-eight (88.4%) patients experienced treatment-related adverse events (TRAE). Because of TRAE, nine (20.9%), 14 (32.6%), and 19 (44.2%) patients required temporary discontinuation, permanent discontinuation, or dose reduction, respectively. CONCLUSIONS: The combination of docetaxel-PM and trastuzumab-pkrb demonstrated promising antitumor activity with a manageable toxicity profile in HER2-positive advanced SDC. PLAIN LANGUAGE SUMMARY: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. SDC shares morphological and histological similarities with invasive ductal carcinoma of breast, which led to an investigation of hormonal receptor and human epidermal growth factor receptor 2 (HER2)/neu expression status in SDC. In this study, patients with HER2-positive SDC were enrolled and treated with combination of docetaxel-polymeric micelle and trastuzumab-pkrb. Promising antitumor activities were shown with objective response rate of 69.8%, disease control rate of 93.0%, median progression-free survival of 7.9 months, median duration of response of 6.7 months, and median overall survival of 23.3 months.

Iron Catalysis of C(sp3)-H Azidation Using a Heteroarene Radical Cation Strategy.

The FeIII(phen)3 catalysis of the benzylic C(sp3)-H azidation of indoles has been investigated. The Fe(III) complex can selectively oxidize indoles to form arene radical cations, which are transformed into benzylic C(sp3) radical intermediates. This strategy exhibits a difference in reactivity between N-heteroarenes and benzene, which is difficult to achieve via direct hydrogen abstraction approaches. Various biorelevant azide precursors were constructed, highlighting the utility of this mild first-row transition-metal catalyst system.

Comparison of Treatment Patterns and Clinical Outcomes by Gender in Locally Advanced Head and Neck Squamous Cell Carcinoma (KCSG HN13-01).

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.

Perception and safety analysis of COVID-19 vaccination in cancer patients: A multicenter, real-world study.

BACKGROUND: Although various coronavirus disease 2019 (COVID-19) vaccines have been delivered to the public worldwide, data on cancer populations are limited. Vaccine hesitancy related to safety concerns is observed among cancer patients. We report the perception of COVID-19 vaccines and their safety profile after vaccination among cancer patients. MATERIALS AND METHODS: Between April and November 2021, a multicenter survey was conducted on 318 patients treated in any hemato-oncology outpatient clinic among three hospitals under the Korea University Medical Center. The medical records of the patients were reviewed to obtain detailed clinical and hematological toxicity data. RESULTS: A perception survey was conducted among 293 patients. Among them, 53.9% were concerned about developing vaccine-related adverse events (VRAEs) and 23.5%, about negative effects on cancer treatment. During the study period, 255 and 186 patients participated in a safety survey after the first and second doses, respectively. After the first dose, 62% of patients reported VRAEs (2.4%, grade 3), whereas 48.9% reported VRAEs (2.7%, grade 3) after the second dose. For both doses, injection-site pain and sore arm pain were the most common VRAEs, followed by myalgia, fatigue, and headache. No grade 4/5 VRAEs were observed, and there were no differences in complete blood count after vaccination. Multivariate analysis revealed female sex, active cancer treatment, and mRNA vaccines as independent risk factors for VRAE development in cancer patients. CONCLUSION: Despite high levels of concern, COVID-19 vaccines were well tolerated by cancer patients, with a safety profile consistent with that of the general population.

Statin use in patients with hormone receptor-positive metastatic breast cancer treated with everolimus and exemestane.

BACKGROUND: We analyzed the effect of statins in patients with hormone receptor-positive (HR+) metastatic breast cancer treated with everolimus + exemestane (EverX). MATERIALS AND METHODS: We conducted a nationwide retrospective cohort study using the National Health Insurance database with patients who received EverX for metastatic breast cancer between 2011 and 2019. RESULTS: Of 224,948 patients diagnosed with breast cancer, 1749 patients who received EverX for at least 30 days were included. Among them, 500 (28.6%) patients were found to take statins with EverX treatment (statin group), and the median duration of this combination was 5.36 months. The median time to treatment duration (TTD) for EverX and the overall survival (OS) were significantly higher in the statin group than in the no-statin group [7.69 vs. 5.06 months, p < 0.001; 45.7 vs. 26.0 months, p < 0.001, respectively]. Multivariable Cox analysis revealed that the use of statins was associated with prolonged TTD [HR = 0.67 (95% CI, 0.59-0.77)] and OS [HR = 0.57 (95% CI, 0.46-0.70)] for EverX even after adjustment for other covariates. CONCLUSION: Statins may have synergistic effects with endocrine therapy with the mTOR inhibitor everolimus, and improve survival in patients with HR+ metastatic breast cancer.

Green-Light-Driven Fe(III)(btz)3 Photocatalysis in the Radical Cationic [4+2] Cycloaddition Reaction.

Green-light-driven FeIII(btz)3 photocatalysis for the radical cationic [4+2] cycloaddition of terminal styrenes and nucleophilic dienes has been investigated. The Fe-MIC (mesoionic carbene) complex forms a ligand-to-metal charge-transfer transition state with relatively high excited-state reduction potentials that can selectively oxidize terminal styrene derivatives. Unique multisubstituted cyclohexenes and structurally complex biorelevant cyclohexenes were constructed, highlighting the usefulness of this mild and practical first-row transition metal complex system.

The risk of cardiovascular disease and stroke in survivors of head and neck cancer in Korea.

BACKGROUND: Head and neck cancer (HNCA) survivors have a high risk of developing cardiovascular disease (CVD) or stroke because of sharing risk factors of disease. Therefore, we investigated the risk of CVD or stroke occurrence among HNCA survivors in Korea based on the Health Insurance Review and Assessment (HIRA) Service claims database. METHODS: We retrieved claims data of patients who were diagnosed with HNCA in 2014-2015 using ICD-10 code and followed up data until 2018. Patients with newly diagnosed with CVD or stroke after HNCA diagnosis during the follow-up period were detected. We analyzed the characteristics of patients with HNCA who were subsequently diagnosed with CVD or stroke. In addition, the risk factors of CVD or stroke occurrence were investigated using Cox proportional hazard regression analysis. RESULTS: Among the 8288 patients with HNCA, 477 and 404 patients were diagnosed with new-onset CVD and stroke, respectively. Patients with hypertension, diabetes mellitus (DM), and hyperlipidemia had a 3.25-fold higher risk of CVD comparing to patients without any underlying disease (95% confidence index [CI], 2.38-4.45) Patients with three underlying diseases had a 2.92-fold higher risk of stroke compared to patients without any underlying disease (95% CI 2.03-4.21). CONCLUSIONS: HNCA survivors with hypertension, DM, and hyperlipidemia should be cautious of the risks of CVD and stroke.