Comparison of Programmed Cell Death Ligand 1Status between Core Needle Biopsy and Surgical Specimens of Triple-Negative Breast Cancer

Purpose@#Pembrolizumab is currently used to treat advanced triple-negative breast cancer (TNBC) and high-risk early TNBC with neoadjuvant chemotherapy (NAC). The tumor-infiltrating lymphocyte (TIL) level and programmed cell death ligand 1 (PDL1) status are predictors of response to NAC and immune checkpoint inhibitor treatment. We aimed to investigate whether the PD-L1 status in core needle biopsies (CNBs) could represent the whole tumor in TNBC. @*Materials and Methods@#A total of 49 patients diagnosed with TNBC who received upfront surgery without NAC between January 2018 and March 2021 were included. The PD-L1 expression (SP142 and 22C3 clones) and TIL were evaluated in paired CNBs and resected specimens. The concordance PD-L1 status and TIL levels between CNBs and resected specimens were analyzed. @*Results@#PD-L1 positivity was more frequently observed in resected specimens. The overall reliability of TIL level in the CNB was good [intraclass correlation coefficient (ICC)=0.847, p<0.001]. The agreements of PD-L1 status were good and fair, respectively (SP142, κ=0.503, p<0.001; 22C3, κ=0.380, p=0.010). As the core number of CNB increased, the reliability and agreement also improved, especially from five tumor cores (TIL, ICC=0.911, p<0.001; PD-L1 [22C3], κ=0.750, p=0.028). Regarding PD-L1 (SP142), no further improvement was observed with ≥5 tumor cores (κ=0.600, p=0.058). @*Conclusion@#CNBs with ≥5 tumor cores were sufficient to represent the TIL level and PD-L1 (22C3) status in TNBC.

Efficacy of Limited Dose Modifications for Palbociclib-Related Grade 3 Neutropenia in Hormone Receptor–Positive Metastatic Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Frequent neutropenia hinders uninterrupted palbociclib treatment in patients with hormone receptor (HR)–positive breast cancer. We compared the efficacy outcomes in multicenter cohorts of patients with metastatic breast cancer (mBC) receiving palbociclib following conventional dose modification or limited modified schemes for afebrile grade 3 neutropenia. @*Materials and Methods@#Patients with HR-positive, human epidermal growth factor receptor 2–negative mBC (n=434) receiving palbociclib with letrozole as first-line therapy were analyzed and classified based on neutropenia grade and afebrile grade 3 neutropenia management as follows: group 1 (maintained palbociclib dose, limited scheme), group 2 (dose delay or reduction, conventional scheme), group 3 (no afebrile grade 3 neutropenia event), and group 4 (grade 4 neutropenia event). The primary and secondary endpoints were progression-free survival (PFS) between groups 1 and 2 and PFS, overall survival, and safety profiles among all groups. @*Results@#During follow-up (median 23.7 months), group 1 (2-year PFS, 67.9%) showed significantly longer PFS than did group 2 (2-year PFS, 55.3%; p=0.036), maintained across all subgroups, and upon adjustment of the factors. Febrile neutropenia occurred in one and two patients of group 1 and group 2, respectively, without mortality. @*Conclusion@#Limited dose modification for palbociclib-related grade 3 neutropenia may lead to longer PFS, without increasing toxicity, than the conventional dose scheme.

Immune-related Adverse Events: Overview and Management Strategies for the Use of Immune Checkpoint Inhibitors

Recent studies on T cell immunology have been instrumental in developing therapies to overcome cancer immune escape, and immune checkpoint inhibitors have emerged as one of the most promising therapeutic tools in advanced cancer patients. Immune checkpoint inhibitors (ICPIs) are monoclonal antibodies that modulate the effects of immune checkpoints. These include cytotoxic T lymphocyte antigen 4 and programmed cell death protein 1, which are co-inhibitory signals responsible for immune suppression. Despite their clinical benefits, ICPIs behave as general immune activators, exerting to several toxic effects called immune-related adverse events attributed to organ-specific inflammation. Here, we review ICPI toxicities, highlighting the importance of their early identification and proper management.

Real-World Analysis of the Efficacy of Rebiopsy and EGFR Mutation Test of Tissue and Plasma Samples in Drug-Resistant Non-Small Cell Lung Cancer

PURPOSE: Standard treatment for cases of non-small cell lung cancer (NSCLC) exhibiting acquired drug resistance includes tumor rebiopsy, epidermal growth factor receptor (EGFR) mutation testing (e.g., for T790M mutations), and the subsequent administration of third-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, rebiopsies are typically invasive, costly, and occasionally not feasible. Therefore, the present study aimed to assess rebiopsy procedures by analyzing real-world data collected by the ASTRIS study of patients with resistant NSCLC. MATERIALS AND METHODS: The present study used statistical models to evaluate data collected by the ASTRIS trial (NCT02474355) conducted at Yonsei Cancer Center, including the rebiopsy success rate, incidence of T790M mutations in collected tissue and plasma samples, and association of administered osimertinib treatment efficacy. RESULTS: In a total of 188 screened patients, 112 underwent rebiopsy. An adequate tumor specimen was obtained in 95 of these patients, the greatest majority of whom (43.8%) were subjected to bronchoscopy. T790M mutations were detected in 53.3% of successfully EGFR-tested rebiopsy samples. A total of 88 patients received osimertinib treatment, and the objective response rate and median progression-free survival time was 44.3% and 32.7 weeks, respectively, among the treated patients overall, but 57.8% and 45.0 weeks, and 35.2% and 20.4 weeks among patients who exhibited T790M-positive tissue (n=45) and plasma (n=54) samples, respectively. CONCLUSION: Approximately 60% of patients in the analyzed real-world cohort were eligible for tissue rebiopsy upon NSCLC progression. Osimertinib activity was higher in patients in whom T790M mutations were detected in tissues rather than in plasma samples.

Prognoses and Clinical Outcomes of Primary and Recurrent Uveal Melanoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Uveal melanoma has a very poor prognosis despite successful local primary tumor treatment. In this study, we investigated prognostic factors that more accurately reflected the likelihood of recurrence and survival and delineated a prognostic model that could effectively identify different risk groups based on initial clinical parameters. MATERIALS AND METHODS: Prognostic factors associated with distant recurrence, recurrence-free survival (RFS), progression-free survival, and overall survival from distant recurrence to death (OS2) were analyzed in 226 patients with stage I-III uveal melanoma who underwent primary local therapy. RESULTS: Forty-nine patients (21.7%) had distant recurrences, which occurred most frequently in the liver (87.7%). In a multivariate analysis, local radiotherapy improved RFS among patients with multiple recurrence risk factors relative to excision (not reached vs. 19.0 months, p=0.004). Patients with BRCA1-associated protein-1 (BAP1)–negative primary tumors showed a longer RFS duration after primary treatments, while those with BAP1-negative metastatic tissues had a shorter OS2 compared to those with BAP1-positive tumors, both not statistically insignificance (RFS: not reached vs. 82.0 months, p=0.258; OS2: 15.7 vs. 24.4 months, p=0.216). Male sex (hazard ratio [HR], 3.79; p=0.012), a short RFS (HR, 4.89; p=0.014), and a largest metastatic tumor linear diameter ≥ 45 mm (HR, 5.48; p=0.017) were found to correlate with worse post-recurrence survival. CONCLUSION: Risk factors could be used to classify uveal melanoma cases and subsequently direct individual treatment strategies. Furthermore, metastasectomy appears to contribute to improved survival outcomes.

Comparison of Melanoma Subtypes among Korean Patients by Morphologic Features and Ultraviolet Exposure

BACKGROUND: Genetic alterations have been identified in melanomas according to different levels of sun exposure. Whereas the conventional morphology-based classification provides a clue for tumor growth and prognosis, the new classification by genetic alterations offers a basis for targeted therapy. OBJECTIVE: The purpose of this study is to demonstrate the biological behavior of melanoma subtypes and compare the two classifications in the Korean population. METHODS: A retrospective chart review was performed on patients found to have malignant melanoma in Severance Hospital from 2005 to 2012. Age, sex, location of the tumor, histologic subtype, tumor depth, ulceration, lymph node invasion, visceral organ metastasis, and overall survival were evaluated. RESULTS: Of the 206 cases, the most common type was acral melanoma (n=94, 45.6%), followed by nonchronic sun damage-induced melanoma (n=43, 20.9%), and mucosal melanoma (n=40, 19.4%). Twenty-one patients (10.2%) had the chronic sun-damaged type, whereas eight patients (3.9%) had tumors of unknown primary origin. Lentigo maligna melanoma was newly classified as the chronic sun-damaged type, and acral lentiginous melanoma as the acral type. More than half of the superficial spreading melanomas were newly grouped as nonchronic sun-damaged melanomas, whereas nodular melanoma was rather evenly distributed. CONCLUSION: The distribution of melanomas was largely similar in both the morphology-based and sun exposure-based classifications, and in both classifications, mucosal melanoma had the worst 5-year survival owing to its tumor thickness and advanced stage at the time of diagnosis.

A Phase II Study with Gemcitabine and Carboplatin in Patients with Advanced Non-small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To evaluate the efficacy and safety of gemcitabine and carboplatin (GC) in the treatment of advanced non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Between November 1999 and April 2001, 34 patients were enrolled in this study. The median age was 66 (range: 52-74) years old and all were male. Sixteen patients demonstrated stage IIIB, 15 stage IV, and 3 recurrence of disease after surgery. Twenty-two patients showed a ECOG performance status of 0 or 1 and 12 had 2. Twenty patients presented with squamous cell carcinoma, 11 adenocarcinoma and 3 unclassified NSCLC. The treatment regimen consisted of intravenous carboplatin AUC of 6 on day 1 and gemcitabine 1,250 mg/m2 on day 1 and 8. The treatment was repeated every 28 days. Toxicities were evaluated according to WHO toxicity criteria. RESULTS: All thirty-four patients were evaluable. Partia responses were observed in 15 patients. The overall response rate was 44% (95% confidence interval: 27-61%) and the median response duration was 26 (range 8-60 ) weeks. The median survival of all patients was 50 (range 8-70 ) weeks. During a total of 144 cycles, granulocytopenia greater than WHO grade 2 occurred in 2%, thrombocytopenia in 2%, and anemia in 3%, respectively. Non- hematologic toxicities were minor and easily controlled. CONCLUSION: A combination chemotherapy of intravenous gemcitabine and carboplatin has a relatively high activity with acceptable toxicities in patients with advanced NSCLC.

Beta2-adrenoceptor Polymorphisms between Asthmatic and Normal Children in Korea / 소아알레르기및호흡기학회지

BACKGROUND: The role of beta2-agonist is still important to control bronchoconstriction in asthma. Polymorphisms at aminoacid positions 16 and 27 of the beta2-adrenoceptor gene are associated with asthma phenotype. Glu 27 allele is associated with negatively with bronchial hyperresponsiveness(BHR) in asthmatic subjects and Gln 27 allele is associated positively with IgE levels, and Gly16 Gln27 haplotype is suggested to be positively associated with BHR in a population study. And Gly16 Gln27 haplotypes are positively associated with nocturnal cough in atopic subjects. To evaluate the association between beta2-adrenoceptor polymorphisms as asthmatic phenotypes, the frequency of beta2-adrenoceptor polymorphsisms at 2 sites(Arg16->Gly 16 and Gln 27 -> Glu 27) were examined in asthmatic and normal children. METHODS: Ninty nine asthmatic children and seventy three normal children were enrolled. Asthma phenotypes were determined by physician and bronchial responsiveness and genotypes of beta2-adrenoceptor polymorphisms were determined with PCR based methods. RESULTS: The polymorphisms at aminoacid 16 and 27 of beta2-adrenoceptor gene was not different between asthmatic and normal children. The haplotype frequency of aminoacid 16 and 27 polymorphisms of beta2-adrenoceptor gene was not different between asthmatic and normal children. Haplotypes of aminoacid 16 and 27 was not associated with total eosinophil count, eosinophil %, and total IgE in asthmatic children. Haplotypes of aminoacid 16 and 27 was not associated with PC20, and response of FEV1 after beta2-agonist in asthmatic children. CONCLUSION: beta2-adrenoceptor polymorphisms is not associated with the expression of asthma, atopy, bronchial hyperresponsiveness, and response to beta2-agonist in Korean children.

Recognition of tabacco health warning labelling in korean family physicians

BACKGROUND: Tobacco health warning labelling as one of the smoking education act has been improved in many countries. But there was no change of tobacco health warning labelling after 1989 in korea. So, for the purpose to help developing new tobacco health warning labelling, we searched the recognition rate of tobacco health warning labelling in family physician and their evaluation of labels which were required form 1976 to 1988, and after 1989 in korea. METHOD: Family physicians who were participated in autumn conference 2000 of the Korean Academy of Family Medicine were questioned about their recognition and evaluation of tobacco health warning labelling required form 1976 to 1988 and after 1989. RESULTS: Response rate to questionnaire was 25%(250/1000), but completely filled response rate included in study was 14.5%(145/1000). The recognition rate of tobacco health warning labelling required in 1976-1988(86.7%) was higher then after 1989(61.4%). When compared by sex, age, and smoking status, each results are similar. Respondents evaluated the tobacco health warning labelling required in 1976-1988 that the information was absolutely small and the vagueness of sentences lead smokers misconceived adverse effect of smoking, and also pointed out that the changed labelling after 1989 is not enough to transmit sufficient information. Respondents recognized that because government provided military personnel with tobacco of free charge, it decreased confidence and warning effect of tobacco health warning labelling(72.4%). Respondents answered active campaign of government against smoking would increase the effect of tobacco health warning labelling(92.4%), but the monopoly of tobacco production by government would support (local)government finance(75.9%). CONCLUSION: New tobacco health warning labelling is needed to increase readability, warning, information against smoking, because present labelling is not recognized well and limited to give information against smoking.

Clinical Value of Thallium-201 Reinjection for the Identification of Myocardial Viability in Patients with Coronary Artery Disease and Left Ventricular Dysfunction

BACKGROUND: The reinjection of a small dose of thallium-201 after stress and delayed imaging often shows new redistribution in the region with persistent defect. The purpose of this study was to determine the incidence of incomplete redistribution on conventional delayed image and to compare the left venticular wall motion abnormality with myocardial viability in patients with coronary artery disease. METHODS: We studied 12 patients with chronic coronary artery disease, using exercise thallium-201 Single Photon Emission Tomopraphy(TI-201 SPECT) and coronary angiopraphy with contrast ventriculography. Patients received 2mCi of thallium intravenously during exercise, redistribution images were performd 4 hour late and a second dose of 1mCi of thallium was injected at rest immediately there after. The three sets of image(stress, redistribution and reinjection) were analyzed. The left ventricular myocardium was divided into 7 segments and regional wall motion was scored on scale from 2(normal) to -1(dyskinesis). RESULTS: 1) The redistribution was obtained in 42.9% of the segments with persistent TI-202 defect on 4 hour delayed image. 2) Myocardial viability was observed in 38.9% of regions with all motion abnormality on contrast ventriculography. 3) The wall motion score was lower in the segments with persistent TI-201 defect on reinjection image than those with transient defect(p<0.05). 4) In 42.9% of the regions with wall motion abnormality on contrast ventrculography before coronary artery bypass graft, normal TI-201 image was observed after coronary artery bypass graft. CONCLUSION: Thallium-201 reinjection image can be used to identify viable myocardium in segments that demonstrate a persistent thallium defect on conventional delayed images patients with chronic coronary artery disease and left venticular dysfuction.

A statistical analysis of methicillin-resistant staphylococcus aureus

No abstract available.